PROMOTER OF THE PROLIFERATION AND INHIBITOR THE APOPTOSE PANKREATI LONG HANS BETA CELLS AND SCREENING OF CANDIDATE CONNECTIONS FOR MEDICINES

PROOF OF A NEUROLOGICAL ILLNESS OR A MALFUNCTION

RAIN PROTEIN.

Method of detecting neurological disease or dysfunction

HUMAN PROISLET PEPTIDE, DERIVATIVES AND ANALOGS THEREOF, AND METHODS OF USING SAME

Human prolslet Peptides (HIP) and HIP analogs and derivatives thereof, derived from or homologous in sequence to the human REG3A protein, chromosome 2p12, are able to induce islet neogenesis from endogenous pancreatic progenitor cells. Human prolslet Peptides are used either alone or in combination with other pharmaceuticals in the treatment of type 1 and type 2 diabetes and other pathologies related to aberrant glucose, carbohydrate, and/or lipid metabolism, insulin resistance, overweight, obesity, polycystic ovarian syndrome, eating disorders and the metabolic syndrome.

REG GENE AND PROTEIN ENCODED BY THE GENE

A rat reg gene specifically expressed in regenerating rat islets, a human reg gene or a gene hybridizable with said genes and the proteins encoded therein, which provide a clue toward the elucidation of the regeneration and proliferation mechanisms of the pancreatic B cells at the molecular level and open a new dimension in the treatment of diabetes.

ASSAY FOR THE DETECTION OF FACTORS THAT MODULATE THE EXPRESSION OF INGAP

A reporter construct contains mammalian INGAP 5'-regulatory region or a fragment thereof, a minimal promoter element from mammalian INGAP or a heterologous promoter, and a reporter gene. The reporter construct can be used to screen for agents which alone or in combination up-regulate or down- regulate reporter gene expression. Alternatively, the reporter construct can be used to screen for agents that bind to the hamster INGAP 5'-regulatory region or a fragment thereof.

GENERATION OF NEW PANCREATIC BETA CELLS

The present invention relates to novel therapies for treatment of new and existing type 1 and type 2 diabetes, PreDiabetes, Latent Autoimmune Diabetes of Adulthood, and diseases of insulin deficiency, beta cell deficiency, insulin resistance and impaired glucose metabolism. In particular, the present invention identifies common peptides within the human Regla, Reglb, Reg3a and Reg4, as signaling peptides for beta cell generation acting through the human Reg Receptor on the surface of human pancreatic extra-islet tissue. This invention identifies a specific binding region of the Reg Receptor from which peptidomimetics and stimulating antibodies have been developed for the generation of new beta cells which may be administered directly to patients with said conditions including type 1 diabetes, type 2 diabetes, PreDiabetes and other conditions of beta cell deficiency, and provides specific methodology for protecting new beta cells generated for usage in type 1 diabetes and Latent Autoimmune ...

INGAP PROTEIN INVOLVED IN PANCREATIC ISLET NEOGENESIS

Cellophane wrapping (CW) of hamster pancreas induces proliferation of duct epithelial cells followed by endocrine cell differentiation and islet neogenesis. Using the mRNA differential display technique a cDNA clone expressed in cellophane wrap but not in control pancreata was identified. Using this cDNA as a probe, a cDNA library was screened and a gene not previously described was identified and named INGAP.

INGAP displacement assays

An antibody is provided which specifically recognizes and binds to INGAP protein. The antibody is used in competitive binding assays for quantitation of INGAP in biological samples. The assay can be performed on a solid support or in a suspension.

A reg protein

КОМПОЗИЦИЯ И СПОСОБ ЛЕЧЕНИЯ ДИАБЕТА

... 1. Фармацевтическая композиция, содержащая полипептид, имеющий пятнадцать аминокислот последовательности SEQ ID NO:3, с рН от 4 до 6. 2. Фармацевтическая композиция по п.1, где данная композиция представляет собой лиофилизированный порошок или раствор. 3. Фармацевтическая композиция по п.1, где композиция имеет рН от 4 до 5. 4. Фармацевтическая композиция по п.1, где полипептид находится в форме, выбранной из фармацевтически приемлемых сложных эфиров, солей и их смесей. 5. Фармацевтическая композиция по п.1, содержащая от 0,1 мг до 300 мг полипептида. 6. Применение фармацевтической композиции по п.1 для производства лекарственного средства для лечения диабета у человека или другого млекопитающего. 7. Применение фармацевтической композиции по п.1 для производства лекарственного средства для регенерации островков Лангерганса, бета клеток поджелудочной железы или установления нормальной физиологической регуляции уровня глюкозы у млекопитающего. 8. Применение фармацевтической композиции по ...

Inhibitors of REGIII proteins as asthma therapeutics

METHOD OF DETECTING NEUROLOGICAL DISEASE OR DYSFUNCTION

This invention relates to a method of detecting and diagnosing neurological diseases or dysfunction using antibodies against a neurological form of Pancreatic Thread Protein (nPTP). Specifically, this invention is directed to a method of diagnosing Alzheimer's Disease, Down's Syndrome, and other neurological diseases or dysfunctions by using monoclonal antibodies and combinations of those monoclonal antibodies to detect nPTP. The invention also relates to the substantially pure form of nPTP. The invention additionally relates to a method of diagnosing pancreatic disease using antibodies against Pancreatic Thread Protein. A102.11.WP 121989 ...

TREATMENT FOR DIABETES

A composition for the treatment of diabetes and a method of use thereof. The composition includes an immunoregulator, preferably Quinoline-3-carboxamide, and a .beta. cell proliferative agent, preferably reg protein. The composition has been shown to be effective in both inhibiting the progression of diabetes, and reversing the course of the disease, in the NOD mouse model.

ПРООСТРОВКОВЫЕ ПЕПТИДЫ ЧЕЛОВЕКА, ИХ ПРОИЗВОДНЫЕ И АНАЛОГИ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

Проостровковые пептиды человека (HIP) и их аналоги и производные, полученные из последовательности человеческого протеина REG3A или гомологичные в плане последовательности человеческому протеину REG3A, хромосома 2р12, способны вызвать островковый неогенез из эндогенных панкреатических клеток-предшественников. Проостровковые пептиды человека используют либо по отдельности, либо в сочетании с другими фармацевтическими препаратами для лечения диабета 1- и 2-го типа или иных патологий, связанных с аберрантным глюкозным, углеводородным и/или липидным метаболизмом, резистентностью к инсулину, избыточным весом, ожирением, синдромом поликистозных яичников, расстройством пищевого поведения и метаболическим синдромом.

ПРООСТРОВКОВЫЕ ПЕПТИДЫ ЧЕЛОВЕКА, ИХ ПРОИЗВОДНЫЕ И АНАЛОГИ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

Проостровковые пептиды человека (HIP) и HIP аналоги и производные, полученные из последовательности человеческого протеина REG3A или гомологичные в плане последовательности человеческому протеину REG3A, хромосома 2р12, способны вызвать островковый неогенез из эндогенных панкреатических клеток-предшественников. Проостровковые пептиды человека используют либо по отдельности, либо в сочетании с другими фармацевтическими препаратами для лечения диабета 1- и 2-го типа или иных патологий, связанных с аберрантным глюкозным, углеводородным и/или липидным метаболизмом, резистентностью к инсулину, избыточным весом, ожирением, синдромом поликистозных яичников, расстройством пищевого поведения и метаболическим синдромом.

DRUGS CONTAINING reg PROTEIN AS ACTIVE INGREDIENT

A cell-proliferating agent and a human sugar level depressant both containing a human or rat reg protein as the active ingredient. Because these drugs enable regeneration of insulin-producing pancreatic beta cells, it is possible to resort to the causal therapy of regeneration and activation of the pancreatic beta cells of a patient with diabetes himself instead of resorting to the conventional symptomatic therapy of insulin administration. In addition, because the reg protein can proliferate Langerhans' islands, the drugs are useful as a human sugar level depressant.

GENEEXPRESSION THE NEURO FILAMENT PROTEINS AND PROOF OF THE ALZHEIME ILLNESS

INGAP PROTEIN AND ITS PARTICIPATION TO THE NEOGENESE OF PANKREATI ISLAND CELLS

Ingap protein involved in pancreatic islet neogenesis

A MONOCLONAL ANTIBODY RECOGNIZING A REG PROTEIN

TARGETING DIMERIZATION OF BAX TO MODULATE BAX ACTIVITY

Methods are provided for identifying an agent that directly modulates a Bcl-2- associated x-protein (BAX) by promoting or disrupting dimerization of the BAX. Agents that directly modulate BAX by affecting dimerization are also provided.

NEURAL THREAD PROTEIN GENE EXPRESSION AND DETECTION OF ALZHEIMER'S DISEASE

The present invention is directed to recombinant hosts expressing novel proteins associated with Alzheimer's Disease, neuroectodermal tumors, malignant astrocytomas, and glioblastomas. This invention is specifically directed to the recombinant hosts and vectors which contain the genes coding for the neuronal thread proteins. This invention is also directed to substantially pure neural thread protein, immunodiagnostic and molecular diagnostic methods to detect the presence of neural thread proteins, and the use of nucleic acid sequences which code for neural thread proteins in gene therapy.

Schwann cell mitogen

A Schwann cell mitogen that is capable of being upregulated during regeneration of neuronal cells or tissue is described. In a particular embodiment, there is provided the use of a protein comprising the sequence presented as SEQ ID No. 1 or a variant, derivative or homologue thereof in the manufacture of a medicament to act as a Schwann cell mitogen.

GENEEXPRESSION THE NEURO FILAMENT PROTEINS AND PROOF OF THE ALZHEIME ILLNESS

HUMAN REG PROTEIN

A human reg protein comprising an amino acid sequence from Ala (lst), Gly (21st), Gln (22nd), Glu (23rd), Ala (24th), Gln (25th), Gln (30th), Ala (3lst) or Ile (33rd) to Asn (165th) among the amino acid sequence as follows: ala gln thr ser ser tyr phe met leu ile ser cys leu met phe leu ser gln ser gln gly gln glu ala gln thr glu leu pro gln ala arg ile ser cys pro glu gly thr asn ala tyr arg ser tyr cys tyr tyr phe asn glu asp arg glu thr trp val asp ala asp leu tyr cys gln asn met asn ser gly asn leu val ser val leu thr gln ala glu gly ala phe val ala ser leu ile lys glu ser gly thr asp asp phe asn val trp ile gly leu his asp pro lys lys asn arg arg trp his trp ser ser gly ser leu val ser tyr lys ser trp gly ile gly ala pro ser ser val asn pro gly tyr cys val ser leu thr ser ser thr gly phe gln lys trp lys asp val pro cys glu asp lys phe ser phe val cys lys phe lys asn and its production.

HUMAN PROISLET PEPTIDE, DERIVATIVES AND ANALOGS THEREOF, AND METHODS OF USING SAME

Human prolslet Peptides (HIP) and HIP analogs and derivatives thereof, derived from or homologous in sequence to the human REG3A protein, chromosome 2p12, are able to induce islet neogenesis from endogenous pancreatic progenitor cells. Human prolslet Peptides are used either alone or in combination with other pharmaceuticals in the treatment of type 1 and type 2 diabetes and other pathologies related to aberrant glucose, carbohydrate, and/or lipid metabolism, insulin resistance, overweight, obesity, polycystic ovarian syndrome, eating disorders and the metabolic syndrome.

REG PROTEIN

INGAP DISPLACEMENT ASSAYS

An antibody is provided which specifically recognizes and binds to INGAP protein. The antibody is used in competitive binding assays for quantitation of INGAP in biological samples. The assay can be performed on a solid support or in a suspension.

INGAP PROTEIN INVOLVED IN PANCREATIC ISLET NEOGENESIS

NEURAL THREAD PROTEIN GENE EXPRESSION AND DETECTION OF ALZHEIMER'S DISEASE

The present invention is directed to recombinant hosts expressing novel proteins associated with Alzheimer's Disease, neuroectodermal tumors, malignant astrocytomas, and glioblastomas. This invention is specifically directed to the recombinant hosts and vectors which contain the genes coding for the neuronal thread proteins. This invention is also directed to substantially pure neural thread protein, immunodiagnostic and molecular diagnostic methods to detect the presence of neural thread proteins, and the use of nucleic acid sequences which code for neural thread proteins in gene therapy.

Nachweis einer neurologischen Krankheit oder einer Funktionsstörung

INGAP-PROTEIN UND DESSEN BETEILIGUNG AN DER NEOGENESE PANKREATISCHER INSELZELLEN

A MONOCLONAL ANTIBODY RECOGNIZING A REG PROTEIN

Neural thread protein gene expression and detection of alzheimer's disease

COMPOSITION AND METHOD FOR TREATING DIABETES

The present invention comprises dosing regimens and formulations of islet cell neogenesis associated protein (INGAP) and INGAP Peptide. The formulation disclosed herein is shown have acceptable stability as a pharmaceutical composition. Further, the formulation is able to regenerate functional islets ...

MODIFIED INGAP PEPTIDES FOR TREATING DIABETES

Novel INGAP peptides for prevention or treatment of diabetes are provided herein, as well as compositions and methods of use thereof. In particular, a 19 amino acid peptide of INGAP which possesses ß-cell neogenesis and insulin potentiating activities and is sufficiently stable for in vivo use is described.

HUMAN PROISLET PEPTIDE, DERIVATIVES AND ANALOGS THEREOF, AND METHODS OF USING SAME

Human prolslet Peptides (HIP) and HIP analogs and derivatives thereof, derived from or homologous in sequence to the human REG3A protein, chromosome 2p12, are able to induce islet neogenesis from endogenous pancreatic progenitor cells. Human prolslet Peptides are used either alone or in combination with other pharmaceuticals in the treatment of type 1 and type 2 diabetes and other pathologies related to aberrant glucose, carbohydrate, and/or lipid metabolism, insulin resistance, overweight, obesity, polycystic ovarian syndrome, eating disorders and the metabolic syndrome.

METHOD OF DETECTING NEUROLOGICAL DISEASE OR DYSFUNCTION

This invention relates to a method of detecting and diagnosing neurological disease or dysfunction using antibodies against a neuro- logical form of Pancreatic Thread Protein (nPTP). Specifically, this invention is directed to a method of diagnosing Alzheimer'.s Disease, Down's Syndrome, and other neurological diseases or dysfunctions by using monoclonal antibodies and combinations of those monoclonal antibodies to detect nPTP. The invention also relates to the substan- tially pure form of nPTP. The invention additionally relates to a method of diagnosing pancreatic disease using antibodies against Pancreatic Thread Protein.

INSULIN INDEPENDENCE AMONG PATIENTS WITH DIABETES UTILIZING AN OPTIMIZED HAMSTER REG3 GAMMA PEPTIDE

Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Neural thread protein gene expression and detection of Alzheimer's disease

Nachweis einer neurologischen Krankheit oder einer Funktionsstörung

Targeting dimerization of BAX to modulate BAX activity

Methods are provided for identifying an agent that directly modulates a Bcl-2- associated x-protein (BAX) by promoting or disrupting dimerization of the BAX. Agents that directly modulate BAX by affecting dimerization are also provided.

HUMAN REG PROTEIN

INHIBITORS OF REGIII PROTEINS AS ASTHMA THERAPEUTICS

COMPOSITIONS AND METHODS OF USING THE HUMAN PROISLET PEPTIDE RECEPTOR

Methods and compositions related to the use of Human proIslet Peptide Receptor (HIP) are disclosed herein. Compositions include peptides and peptidomimetics capable of binding the HIP receptors. Methods include screening assays for ligands of receptors and proteins involved in islet cell signaling.

A reg protein

A new reg protein is provided. The reg protein has an amino acid sequence beginning with the glutamine residue at the 20th position from the amino terminus and terminating with the asparagine residue at the 165th position in Figure 1, or an amino acid sequence containing an additional methionine residue at the amino terminus of said amino acid sequence extending from the glutamine residue to the asparagine residue.

Medicament

MONOCLONAL ANTIBODY RECOGNIZING A REG PROTEIN

A monoclonal antibody recognizing a reg protein and a hybridoma producing the monoclonal antibody are provided. Also, a method for the assay of a reg protein using the monoclonal antibody is provided.

HUMAN PROISLET PEPTIDE, DERIVATIVES AND ANALOGS THEREOF, AND METHODS OF USING SAME

Human prolslet Peptides (HIP) and HIP analogs and derivatives thereof, derived from or homologous in sequence to the human REG3A protein, chromosome 2p12, are able to induce islet neogenesis from endogenous pancreatic progenitor cells. Human prolslet Peptides are used either alone or in combination with other pharmaceuticals in the treatment of type 1 and type 2 diabetes and other pathologies related to aberrant glucose, carbohydrate, and/or lipid metabolism, insulin resistance, overweight, obesity, polycystic ovarian syndrome, eating disorders and the metabolic syndrome.

AGENTS FOR PROLIFERATING PANCREATIC BETA-CELLS OF THE ISLETS OF LANGERHANS, AGENTS FOR SUPPRESSING APOPTOSIS OF SAID CELLS, AND SCREENING OF CANDIDATE COMPOUNDS FOR THESE AGENTS

It is indicated that the expression of Reg gene in .szlig. cells can be remarkably induced and thus the proliferation of .szlig. cells can be promoted by using an inflammation transmitter IL-6 together with glucocorticoid. It is also indicated that HGF inhibits apoptosis induced by Reg protein and that IL- 6 and glucocorticoid induce the expression of HGF gene in cells. PARP inhibitors such as nicotinic acid amide and 3-aminobenzamide further enhance the induction of the expression of these genes. Moreover, the expression induction mechanism is analyzed by using the promoter regions of Reg gene and HGF gene and a method of efficiently screening candidate compounds for these gene expression inducers is developed.

PROMOTOR DER PROLIFERATION UND INHIBITOR DER APOPTOSE PANKREATISCHER LANGERHANS BETA-ZELLEN UND SCREENING VON ANWÄRTER-VERBINDUNGEN FÜR MEDIKAMENTE

Ingap protein involved in pancreatic islet neogenesis

REG PROTEIN

A new reg protein is provided. The reg protein has an amino acid sequence beginning with the glutamine residue at the 20th position from the amino terminus and terminating with the asparagine residue at the 165th position in Figure 1, or an amino acid sequence containing an additional methionine residue at the amino terminus of said amino acid sequence extending from the glutamine residue to the asparagine residue.

INGAP PROTEIN INVOLVED IN PANCREATIC ISLET NEOGENESIS

Cellophane wrapping (CW) of hamster pancreas induces proliferation of duct epithelial cells followed by endocrine cell differentiation and islet neogenesis. Using the mRNA differential display technique a cDNA clone expressed in cellophane wrap but not in control pancreata was identified. Using this cDNA as a probe, a cDNA library was screened and a gene not previously described was identified and named INGAP.

ASSAY FOR THE DETECTION OF FACTORS THAT MODULATE THE EXPRESSION OF INGAP

A reporter construct contains mammalian INGAP 5'-regulatory region or a fragment thereof, a minimal promoter element from mammalian INGAP or a heterologous promoter, and a reporter gene. The reporter construct can be used to screen for agents which alone or in combination up-regulate or down-regulate reporter gene expression. Alternatively, the reporter construct can be used to screen for agents that bind to the hamster INGAP 5'-regulatory region or a fragment thereof. © KIPO & WIPO 2007 ...

Medicament

Treatment for diabetes

A REG PROTEIN

PROTEINS INCREASING PANCREATIC BETA CELL NUMBER AND METHODS OF USE

Disclosed herein are bacterial proteins that increase pancreatic beta (ß) cell number and/or proliferation, methods of increasing ß cell number and/or proliferation using such proteins, and methods of treating or inhibiting diabetes in a subject by administering such proteins to the subject. In some embodiments, the protein has at least 80% sequence identity to the amino acid sequence set forth as any one of SEQ ID NOs: 1-7, or fragments thereof. Recombinant vectors including a nucleic acid encoding the protein (such as a nucleic acid encoding a protein with at least 80% sequence identity to any one of SEQ ID NOs: 1-7 or fragments thereof) operably linked to a heterologous promoter are also disclosed. Also disclosed are methods of identifying compounds that increase ß cell number and/or proliferation by determining the effect of test compounds on ß cell number or proliferation in zebrafish pancreas.

NEURAL THREAD PROTEIN GENE EXPRESSION AND DETECTION OF ALZHEIMER`S DISEASE

Neural thread protein gene expression and detection of Alzheimer's disease

The present invention is directed to recombinant hosts expressing proteins associated with Alzheimer's Disease, neuroectodermal tumors, maligant astrocytomas, and glioblastomas. This invention is specifically directed to the recombinant hosts and vectors which contain the genes coding for the neuronal thread proteins. This invention is also directed to substantially pure neural thread protein, immunodiagnostic and molecular diagnostic methods to detect the presence of neural thread proteins, and the use of nucleic acid sequences which code neural thread proteins in gene therapy.

MEDICAMENT

A Schwann cell mitogen that is capable of being upregulated during regeneration of neuronal cells or tissue is described. In a particular embodiment, there is prov ided the use of a protein comprising the sequence presented as SEQ ID No. 1 or a variant, derivative or homologue thereof in the manufacture of a medicament to act as a Schwann cell mitogen.

Medicament

Neural thread protein gene expression and detection of alzheimer's disease

NEURAL THREAD PROTEIN GENE EXPRESSION AND DETECTION OF ALZHEIMER'S DISEASE

The present invention is directed to recombinant hosts expressing novel proteins associated with Alzheimer's Disease, neuroectodermal tumors, malignant astrocytomas, and glioblastomas. This invention is specifically directed to the recombinant hosts and vectors which contain the genes coding for the neuronal thread proteins. This invention is also directed to substantially pure neural thread protein, immunodiagnostic and molecular diagnostic methods to detect the presence of neural thread proteins, and the use of nucleic acid sequences which code for neural thread proteins in gene therapy.

Medicament

Medicament

METHOD OF DETECTING NEUROLOGICAL DISEASE OR DYSFUNCTION

Regulatory sequences for modulation of INGAP expression and reporter constructs

A an isolated mammalian INGAP 5''-regulatory region comprising at least about nucleotides 1-3137 of SEQ ID NO: 2 (SEQ ID NO: 23).

Assay for the detection of factors that modulate the expression of INGAP

A reporter construct contains mammalian INGAP 5′-regulatory region or a fragment thereof, a minimal promoter element from mammalian INGAP or a heterologous promoter, and a reporter gene. The reporter construct can be used to screen for agents which alone or in combination up-regulate or down-regulate reporter gene expression. Alternatively, the reporter construct can be used to screen for agents that bind to the hamster INGAP 5′-regulatory region or a fragment thereof.

Reg-Gen und dadurch kodiertes Protein.

ANALYSE PERMETTANT DE DETECTER DES FACTEURS QUI MODULENT L'EXPRESSION D'INGAP

Neural thread protein gene expression and detection of alzheimer's disease

A REG PROTEIN

Pancreatic langerhans beta cell proliferation promoter and apoptosis inhibitor, and screening of candidate compounds for the e drugs

PEPTIDES, DERIVATIVES AND ANALOGS THEREOF, AND METHODS OF USING SAME

Agents for proliferating pancreatic beta-cells of the islets of langerhans, agents for suppressing apoptosis of said cells, and screening of candidate compounds for these agents

PANCREATIC LANGERHANS β CELL PROLIFERATION PROMOTER AND APOPTOSIS INHIBITOR, AND SCREENING OF CANDIDATE COMPOUNDS FOR THE E DRUGS

It is indicated that the expression of Reg gene in ß cells can be remarkably induced and thus the proliferation of ß cells can be promoted by using an inflammation transmitter IL-6 together with glucocorticoid. It is also indicated that HGF inhibits apoptosis induced by Reg protein and that IL-6 and glucocorticoid induce the expression of HGF gene in cells. PARP inhibitors such as nicotinic acid amide and 3-aminobenzamide further enhance the induction of the expression of these genes. Moreover, the expression induction mechanism is analyzed by using the promoter regions of Reg gene and HGF gene and a method of efficiently screening candidate compounds for these gene expression inducers is developed.

PROTEINS INCREASING PANCREATIC BETA CELL NUMBER AND METHODS OF USE

Methods of identifying compounds that increase β cell number and/or proliferation by determining the effect of compounds on β cell number or proliferation in zebrafish pancreas are provided.

Proteins increasing pancreatic β cell number and methods of use

Methods of identifying compounds that increase β cell number and/or proliferation by determining the effect of compounds on β cell number or proliferation in zebrafish pancreas are provided.

A monoclonal antibody recognizing a reg protein

GENEEXPRESSION DER NEUROFILAMENTPROTEINE UND NACHWEIS DER ALZHEIMESCHEN ERKRANKUNG

Generation of new pancreatic beta cells

The present invention relates to novel therapies for treatment of new and existing type 1 and type 2 diabetes, PreDiabetes, Latent Autoimmune Diabetes of Adulthood, and diseases of insulin deficiency, beta cell deficiency, insulin resistance and impaired glucose metabolism. In particular, the present invention identifies common peptides within the human Regla, Reglb, Reg3a and Reg4, as signaling peptides for beta cell generation acting through the human Reg Receptor on the surface of human pancreatic extra-islet tissue. This invention identifies a specific binding region of the Reg Receptor from which peptidomimetics and stimulating antibodies have been developed for the generation of new beta cells which may be administered directly to patients with said conditions including type 1 diabetes, type 2 diabetes, PreDiabetes and other conditions of beta cell deficiency, and provides specific methodology for protecting new beta cells generated for usage in type 1 diabetes and Latent Autoimmune ...

Medicament

Method of detecting neurological disease or dysfunction

HUMAN REG PROTEIN

INSULIN INDEPENDENCE AMONG PATIENTS WITH DIABETES UTILIZING AN OPTIMIZED HAMSTER REG3 GAMMA PEPTIDE

Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

INGAP PROTEIN INVOLVED IN PANCREATIC ISLET NEOGENESIS

Cellophane wrapping (CW) of hamster pancreas induces proliferation of duct epithelial cells followed by endocrine cell differentiation and islet neogenesis. Using the mRNA differential display technique a cDNA clone expressed in cellophane wrap but not in control pancreata was identified. Using this cDNA as a probe, a cDNA library was screened and a gene not previously described was identified and named INGAP.

Composição e método para tratamento de diabetes

Insulin independence among patients with diabetes utilizing an optimized hamster REG3 gamma peptide

Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

PEPTIDES, DERIVATIVES AND ANALOGS THEREOF, AND METHODS OF USING SAME

Human prolslet Peptides (HIP) and HIP analogs and derivatives thereof, derived from or homologous in sequence to the human REG3A protein, chromosome 2p12, are able to induce islet neogenesis from endogenous pancreatic progenitor cells. Human prolslet Peptides are used either alone or in combination with other pharmaceuticals in the treatment of type 1 and type 2 diabetes and other pathologies related to aberrant glucose, carbohydrate, and/or lipid metabolism, insulin resistance, overweight, obesity, polycystic ovarian syndrome, eating disorders and the metabolic syndrome.

INHIBITORS OF REGIII PROTEINS AS ASTHMA THERAPEUTICS

Methods of screening for agents for treating asthma are provided. The methods involve screening for agents that decrease the production or activity of a RegIII protein that has been discovered herein to play a role in producing the symptoms and pathological complications involved in asthma. Methods of treating asthma, as well as screening for and treating with inhibitors of a RegIII protein are also provided.

inhibitors as therapeutic [...][...] for asthma

GENERATION OF NEW PANCREATIC BETA CELLS

The present invention relates to novel therapies for treatment of new and existing type 1 and type 2 diabetes, PreDiabetes, Latent Autoimmune Diabetes of Adulthood, and diseases of insulin deficiency, beta cell deficiency, insulin resistance and impaired glucose metabolism. In particular, the present invention identifies common peptides within the human Regla, Reglb, Reg3a and Reg4, as signaling peptides for beta cell generation acting through the human Reg Receptor on the surface of human pancreatic extra-islet tissue. This invention identifies a specific binding region of the Reg Receptor from which peptidomimetics and stimulating antibodies have been developed for the generation of new beta cells which may be administered directly to patients with said conditions including type 1 diabetes, type 2 diabetes, PreDiabetes and other conditions of beta cell deficiency, and provides specific methodology for protecting new beta cells generated for usage in type 1 diabetes and Latent Autoimmune ...

Ingap protein involved in pancreatic islet neogenesis

Cellophane wrapping (CW) of hamster pancreas induces proliferation of duct epithelial cells followed by endocrine cell differentiation and islet neogenesis. Using the mRNA differential display technique a cDNA clone expressed in cellophane wrapped but not in control pancreata was identified. Using this cDNA as a probe, a cDNA library was screened and a gene not previously described was identified and named INGAP.

Cell Penetrating Peptide Conjugates for Delivering of Nucleic Acids into a Cell

The invention provides cell penetrating peptide-nucleic acid conjugates having the formula P-L-N, wherein P is a cell penetrating peptide, N is a nucleic acid, preferably an oligonucleotide and more preferably a siRNA, and L is a hydrophilic polymer, preferably a polyethylene glycol (PEG)-based linker linking P and N together. Compositions, methods of use and methods for producing such conjugates are also disclosed.

Pharmaceutical composition for treating or preventing cancer by inducing dendritic cell-like differentiation from monocytes to improve anticancer immune activity

According to the present invention, a composition for inducing or activating dendritic cell-like cells so as to treat or prevent cancer by immunotherapy is provided. Specifically, the following is provided: an agent for activating cancer immunity, which comprises, as an active ingredient, the following REIC protein: (a) a protein consisting of the amino acid sequence shown in SEQ ID NO: 2; or (b) a protein consisting of an amino acid sequence derived from the amino acid sequence shown in SEQ ID NO: 2 by substitution, deletion, or addition of one or more amino acid(s) and having the activity of inducing differentiation from monocytes into dendritic cell-like cells.

Compositions and methods for diagnosing prostate cancer based on detection of slc45a3-elk4 fusion transcript

RNA transcripts representing a fusion of a human SLC45A3 nucleic acid and a human ELK4 nucleic acid that are associated with prostate cancer are described. Compositions and methods useful for detection of fusion transcripts of human SLC45A3 and ELK4 genetic sequences associated with cancer and useful for cancer therapy are provided.

RBM3 in Testicular Cancer Diagnostics and Prognostics

The present disclosure provides a method for determining whether a mammalian subject belongs to a first or a second group, wherein subjects of the first group have a higher risk of having a testicular disorder than subjects of the second group, comprising the steps of: evaluating an amount of RBM3 protein or RBM3 mRNA in at least part of an earlier obtained sample comprising biological material from a testicle of said subject and determining a sample value corresponding to the evaluated amount; comparing said sample value with a predetermined reference value; and if said sample value is higher than said reference value, concluding that the subject belongs to the first group; and if said sample value is lower than or equal to said reference value, concluding that the subject belongs to the second group. Further, a prognostic method for testicular cancer is provided, as well as means and uses with prognostic and diagnostic applications.

Lung cancer diagnostic polypeptide, method for detecting lung cancer, and method for evaluating therapeutic effect

A novel biomarker for use in lung cancer diagnosis is provided.

Novel autography regulators atg14l and rubicon

The present invention provides for up- and down-regulation of cellular autophagy, e.g., for treating cancer or neurological disease. The invention results, in part, from discovery of two novel proteins, ATG14L (previously called “BISC”) and Rubicon (previously called “BIRC”), which bind to a Class III phophatidylinositol 3′-kinase (PI3K)/Vps34-Beclin 1 autophagic complex. ATG14L and Rubicon each regulate autophagic activity in an opposing manner. ATG14L and Rubicon can be used, for example, to increase/decrease autophagic activity, to increase/decrease PI3K/Vps34 kinase activity, and in so doing, treat diseases and disorders, such as cancer, neurodegenerative disease, stroke, metabolic disease, and age-related disease. ATG14L can increase autophagic activity and PI3K/Vps34 kinase activity; and Rubicon can decrease autophagic activity and PI3K/Vps34 kinase activity.

Hair treatment composition with naturally - derived peptide identical to human hair

A hair treatment composition containing at least one peptide identical to human hair, where preferably the peptide is synthesized from naturally-derived amino acids and can serve as a natural alternative to the commonly used human or animal derived (wool) keratin peptides.

Immunogenic epitopes of ngep antigen

The invention provides a peptide comprising a human cytolytic T lymphocyte (CTL) epitope from the human tumor-associated antigen (TAA) New Gene Expressed in Prostate (NGEP), which can be used in vaccine prevention or therapy of prostate cancer, as well as a nucleic acid encoding the peptide, a vector comprising the nucleic acid, a cell comprising the peptide, nucleic acid, or vector, and compositions thereof.

Psca: prostate stem cell antigen and uses thereof

The invention provides a novel prostate cell-surface antigen, designated Prostate Stem Cell Antigen (PSCA), which is widely over-expressed across all stages of prostate cancer, including high grade prostatic intraepithelial neoplasia (PIN), androgen-dependent and androgen-independent prostate tumors.

Stabilized alpha helical peptides and uses thereof

Novel polypeptides and methods of making and using the same are described herein. The polypeptides include cross-linking (“hydrocarbon stapling”) moieties to provide a tether between two amino acid moieties, which constrains the secondary structure of the polypeptide. The polypeptides described herein can be used to treat diseases characterized by excessive or inadequate cellular death.

Compositions comprising angiogenic factors and methods of use thereof

The present invention provides recombinant Listeria strains comprising an angiogenic factor, recombinant polypeptides comprising an angiogenic factor operatively linked to a polypeptide comprising a PEST-like sequence, recombinant nucleotide molecules encoding same, related vaccines, and immunogenic and therapeutic methods utilizing same.

Ttk peptides and vaccines including the same

Peptide vaccines against cancer are described herein. In particular, epitope peptides derived from the TTK gene that elicit CTLs are provided. Antigen-presenting cells and isolated CTLs that target such peptides, as well as methods for inducing the antigen-presenting cell, or CTL are also provided. The present invention further provides pharmaceutical compositions containing as active ingredients peptides derived from TTK or polynucleotides encoding the peptides. Furthermore, the present invention provides methods for the treatment and/or prophylaxis (i.e., prevention) of cancers (tumors), and/or the prevention of postoperative recurrence thereof, as well as methods for inducing CTLs, methods for inducing anti-tumor immunity, using the peptides derived from TTK, polynucleotides encoding the peptides, or antigen-presenting cells presenting the peptides, or the pharmaceutical compositions of the present invention.

Foxm1 peptides and vaccines containing the same

The present invention provides isolated peptides having the amino acid sequence of SEQ ID NO: 34 or fragments thereof, which bind to HLA antigen and induce cytotoxic T lymphocyte (CTL). The present invention further provides peptides which include one, two, or several amino acid insertions, substitution or addition to the aforementioned peptides or fragments, but still have the cytotoxic T cell inducibility. Further provided are nucleic acids encoding any of these aforementioned peptides as well as pharmaceutical substances or compositions including any of the aforementioned peptides or nucleic acids. The peptides, nucleic acids, pharmaceutical substances or compositions of the present invention may be used for treating cancer or tumor.

P53 fusion proteins and methods of making and using thereof

Biologically active tetrameric p53 proteins and p53 fusion proteins are provided. These proteins may be generated and refolded into tetrameric form using denatured proteins produced from E. coli . Therapeutic uses of p53 proteins and p53 fusion proteins are also provided.

Phosphopeptides as melanoma vaccines

We characterized a total of 175 HLA-DR-associated phosphopeptides using sequential affinity isolation, biochemical enrichment, mass spectrometric sequencing and comparative analysis. Many were derived from source proteins which may have roles in cancer development, growth and metastasis. Most were expressed exclusively by either melanomas or transformed B cells, suggesting the potential to define cell type-specific phosphatome “fingerprints”. We generated HLA-DRβ1*0101-restricted CD4 + T cells specific for a phospho-MART-1 peptide identified in two melanoma cell lines. These T cells showed specificity for phosphopeptide-pulsed antigen presenting cells as well as for intact melanoma cells. MHC II-restricted phosphopeptides recognizable by human CD4 + T cells are potential targets for cancer immunotherapy.

Novel human p53 splice variant displaying differential transcriptional activity

Novel human p53 splice variant displaying differential transcriptional activity Described is a nucleic acid molecule encoding a p53 variant characterized in that it is capable of transactivating the p21- and 14-3-3σ-promoter but not the mdm2-, bax- and PIG3-promoter. Preferably, in said p53 variant exon 7, exon 8 and/or exon 9 are partially or entirely deleted. Finally, means for inhibiting the activity of this p53 variant are described which are useful for the therapy of cancer.

Treatment of cancer and compositions

The invention discloses a method of identifying a gene associated with stage III primary cancer or lymph node metastasis. The genes so identified include CAV1, CST3, LIMK1, MMP2, MMP15, VEGF, ETV4, MMP9, PIK3C2B, and SERPIN1. Also disclosed are methods for diagnosis, prognosis, and treatment of cancer. The invention further discloses compositions for preventing and treating diseases.

Nucleic acids and corresponding proteins entitled 158p3d2 useful in treatment and detection of cancer

A novel gene 158P3D2 and its encoded protein, and variants thereof, are described wherein 158P3D2 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 158P3D2 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 158P3D2 gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 158P3D2 can be used in active or passive immunization.

Immunodominant mhc dr52b restricted ny-eso-1 epitopes, mhc class ii monomers and multimers, and uses thereof

Immunostimulatory NY-ESO-1 epitopes recognized by MHC-DRB3*0202 (DR52b) or DRB1*0101 (DR1) restricted T cells are described. Methods for their use in diagnostic and therapeutic approaches are also provided. Further, methods for the generation and isolation of MHC class II molecules, either “empty” or peptide-loaded, are provided. Methods for the assembly of MHC class II multimers, for example, tetramers, are also provided. Methods for the detection of T cells binding to specific peptide-loaded MHC class II molecules are also described herein.

Immunogenic pote peptides and methods of use

POTE has recently been identified as a tumor antigen expressed in a variety of human cancers, including colon, ovarian, breast, prostate, lung and pancreatic cancer. Described herein are immunogenic POTE polypeptides, including modified POTE polypeptides, that bind MHC class I molecules. The immunogenic POTE polypeptides are capable of inducing an immune response against POTE-expressing tumor cells. Thus, provided herein is a method of eliciting an immune response in a subject, such as a subject having a type of cancer that expresses POTE.

Method and composition for generating programmed cell death resistant algal cells

The present invention provides transgenic algal cells resistant to programmed cell death (PCD) and methods and compositions useful in generating such cells. Specifically, the invention utilizes expression of one or more mammalian anti-apoptotic genes in algal cells to promote resistance to PCD, which is useful for stress tolerance and increased cell viability and biomass production during cultivation.

Tumour Markers

A method of determining the immune response of a mammal to circulating tumour marker proteins is described in which a sample of bodily fluid, for example plasma or serum, is contacted with a panel of two or more distinct tumour marker antigen. The presence of complexes between the tumour marker antigens and any autoantibodies to the antigens present in the sample are detected and provide an indication of an immune response to a circulating tumour marker protein. The method is useful for the diagnosis of cancer, particularly for identifying new or recurrent cancer in an otherwise assymptomatic patient.

Vaccine for Tumor Immunotherapy

The present invention relates to a vaccine comprising dendritic cells and bacterial ghosts for tumor immunotherapy. 1. A composition comprising:(i) antigen-presenting cells;(ii) at least one tumor-associated antigen; and,(iii) bacterial ghosts.2. The composition of for use as vaccine for tumor immunotherapy.3. The composition of claim 1 , wherein the antigen-presenting cells comprise monocytes.4. The composition of claim 1 , wherein the antigen-presenting cells comprise dendritic cells.5. The composition of claim 1 , comprising one or more tumor lysates.6. The composition of wherein the bacterial ghosts are obtained from bacterial cells comprising a gene encoding a lytic protein.7. The composition of claim 1 , wherein the bacterial ghosts have been treated with β-propiolactone.8. The composition of claim 1 , wherein the bacterial ghosts are from Gram-negative bacteria.9E. coli.. The composition of claim 8 , wherein the bacterial ghosts from Gram-negative bacteria are from10E. Coli. The composition of claim 8 , wherein the bacterial ghosts from Gram-negative bacteria are from Nissle 1917.11. The composition of claim 1 , wherein the bacterial ghosts are loaded with an activator or silencer of the immune system claim 1 , a pharmaceutical agent and/or DNA.12. The composition of claim 1 , wherein the bacterial ghosts carry recombinant tumor-associated antigens.13. The composition of claim 12 , wherein the bacterial ghosts are loaded with tumor-associated antigens.14. The composition of claim 12 , wherein the bacterial ghosts are derived from bacteria recombinantly expressing tumor-associated antigens.15. The composition of claim 1 , comprising from 1 to 10 claim 1 ,000 claim 1 , or from 10 to 1 claim 1 ,000 bacterial ghosts per antigen-presenting cell.16. The composition of claim 1 , comprising 1 to 10 million antigen-presenting cells per dose.17. The composition of claim 1 , wherein the antigen-presenting cells induce tumor-antigen recognition and tumor-specific killing ...

Cancer peptide vaccine

A composition for treating cancer, comprising 6 to 13 peptides derived from tumor antigens, wherein the composition is used in the manner that antibodies to the respective peptides in the peripheral blood of a patient are measured and peptides to which antibodies are positive are selected and administered to the patient, and a peptide selection method.

COMPOSITIONS AND METHODS FOR ASSESSING AND TREATING A PRECURSOR LESION AND/OR ESOPHAGEAL CANCER

One aspect of the present disclosure relates to a method for predicting a subject's risk of developing an esophageal cancer, a precursor lesion, or both. One step of the method includes obtaining a biological sample from the subject. Next, the presence of at least one germline mutation is determined in the biological sample. The subject is at an increased risk of an esophageal cancer, a precursor lesion, or both, where the presence of at least one germline mutation is determined. 1. An isolated nucleic acid molecule comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO: 7 , SEQ ID NO: 8 , SEQ ID NO: 13 and SEQ ID NO: 17.2. An isolated polypeptide molecule comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 9 , SEQ ID NO: 10 , SEQ ID NO: 14 and SEQ ID NO: 18.3. An isolated antibody that specifically binds to a polypeptide molecule having an amino acid sequence selected from the group consisting of SEQ ID NO: 9 , SEQ ID NO: 10 , SEQ ID NO: 14 and SEQ ID NO: 18.4. A method for predicting a subject's risk of developing an esophageal cancer , a precursor lesion , or both , the method comprising the steps of:obtaining a biological sample from the subject;determining in the biological sample the presence of at least one germline mutation; anddetermining that the subject is at increased risk of an esophageal cancer, a precursor lesion, or both, due the presence of the at least one germline mutation.5. The method of claim 4 , wherein the precursor lesion is Barrett's esophagus (BE) and the esophageal cancer is esophageal adenocarcinoma (EAC).6. The method of claim 4 , wherein the at least one germline mutation is present in one or more genes selected from the group consisting of macrophage scavenger receptor 1 (MSR1) claim 4 , activating signal cointegrator 1 complex subunit 1 (ASCC1) claim 4 , and collagen triple-helix repeat-containing 1 (CTHRC1).7. The method of claim 6 , wherein the at least one germline ...

Ssx-2 peptide analogs

Some embodiments relate to analogs of peptides corresponding to class I MHC-restricted T cell epitopes and methods for their generation. These analogs can contain amino acid substitutions at residues that directly interact with MHC molecules, and can confer improved, modified or useful immunologic properties. Additionally classes of analogs, in which the various substitutions comprise the non-standard residues norleucine and/or norvaline, are disclosed.

Genes Differentially Expressed in Breast Cancer

A polynucleotide sequence as shown in SEQ ID NO:1 is associated with metastatic potential of cancer cells, especially breast cancer cells. Methods are provided for determining the risk of metastasis of a tumor, by determining whether a tissue sample from a tumor expresses a polypeptide or mRNA encoded by a polynucleotide as shown in SEQ ID NO:1. Also provided are therapeutic methods and compositions.

BNIP3 ISOFORMS AND METHODS OF USE

The present invention provides isolated splice variants of Bnip3 and isolated polynucleotides encoding the splice variants. Also provided are isolated polypeptides present at the carboxy-terminus of Bnip3 splice variants, and antibody that specifically binds Bnip3 splice variants and/or the carboxy-terminus of Bnip3 splice variants. The present invention further provides methods of altering cellular apoptosis, cellular necrosis, cellular autophagy, or the combination thereof. For instance, the methods may include changing the amount of a Bnip3 splice variant or a carboxy-terminal region of a Bnip3 splice variant in a cell. Also provided herein are methods for determining whether death of cells in a tissue can be altered, methods for evaluating treatment options for a subject, and methods for identifying a compound that alters the amount or activity of a Bnip3 splice variant in a cell. 1. A method for modifying apoptosis , necrosis , autophagy , or the combination thereof , of a cell comprising:expressing in a cell a polypeptide having Bnip3 antagonist activity, wherein (i) the amino acid sequence of the polypeptide and the amino acid sequence of SEQ ID NO:2 have at least 84% identity, or (ii) the amino acid sequence of the polypeptide and the amino acid sequence of SEQ ID NO:7 have at least 80% identity,wherein apoptosis, necrosis, autophagy, or the combination thereof, is modified in the cell compared to a control cell.2. The method of wherein the expressing comprises introducing the polypeptide into the cell.3. The method of wherein the expressing comprises introducing into the cell a polynucleotide encoding the polypeptide.4. The method of wherein the polynucleotide comprises a vector.5. The method of wherein the cell is ex vivo.6. The method of wherein the cell is in vivo.7. An isolated polypeptide having Bnip3 antagonist activity claim 1 , wherein the polypeptide comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 2 or at least ...

PUF-A AND RELATED COMPOUNDS FOR TREATMENT OF RETINOPATHIES AND SIGHT-THREATENING OPHTHALMOLOGIC DISORDERS

Methods and compositions for treating retinal diseases comprising therapeutic amounts of a compound selected from a normal Puf-A gene product, an active polypeptide fragment thereof, an analog thereof or a peptidomimetic thereof. Vectors, including AAV vectors comprising the therapeutic compound are provided. Puf-A compositions suitable for subretinal, intravitreal, topical, subconjunctival, retrobulbar, periocular, suprachoroidal, or intraocular administration are provided. Methods for screening siRNA, RNAi and shRNA, small molecules and monoclonal antibodies that inhibit Puf-A target activity and reduce apoptosis are provided. 1. A method for treating a retinal disease , the method comprising:providing at least a portion of a Puf-A gene suitable for expression of a Puf-A therapeutic protein;incorporating the gene into a vector;transfecting the vector into at least one ocular cell; andexpressing at least the portion of the therapeutic Puf-A protein in at least one ocular cell to thereby treat the retinal disease.2. The method of claim 1 , wherein the retinal disease is selected from the group consisting of progressive ganglion cell degeneration claim 1 , retinitis pigmentosa claim 1 , retinal ischemia claim 1 , Leber's hereditary optic neuropathy claim 1 , age-related macular degeneration claim 1 , diabetic retinopathy claim 1 , open angle glaucoma claim 1 , and glaucoma.3. The method of claim 1 , wherein the step of incorporating the gene into the vector comprises incorporating the gene into a viral vector.4. The method of claim 3 , wherein the vector is selected from the group consisting of adeno-associated viral vector claim 3 , adenoviral vector claim 3 , retroviral vector claim 3 , herpes viral vector claim 3 , parvoviral vector claim 3 , and lentiviral vector.5. The method of claim 3 , wherein the viral vector is an adeno-associated viral vector (AAV).6. The method of claim 1 , comprising transfecting a human retinal cell with the vector.7. The method of ...

Stabilized Compounds Having Secondary Structure Motifs

The present invention provides novel stabilized crosslinked compounds having secondary structure motifs, libraries of these novel compounds, and methods for the synthesis of these compounds libraries thereof. The synthesis of these novel stabilized compounds involves (1) synthesizing a peptide from a selected number of natural or non-natural amino acids, wherein said peptide comprises at least two moieties capable of undergoing reaction to promote carbon-carbon bond formation; and (2) contacting said peptide with a reagent to generate at least one crosslinker and to effect stabilization of a secondary structure motif. The present invention, in a preferred embodiment, provides stabilized p53 donor helical peptides. Additionally, the present invention provides methods for disrupting the p53/MDM2 binding interaction comprising (1) providing a crosslinked stabilized α-helical structure; and (2) contacting said crosslinked stabilized α-helical structure with MDM2.

Early Diagnosis and Novel Treatment of Cancer

The present invention relates to novel therapies for treatment and new biomarkers for earlier detection of pancreatic and other cancers. In particular, the present invention identifies Reg1α and Reg3α, and other members of the Reg protein family, as signaling proteins for a receptor on the surface of human cancer cells, Megi, and the downstream pathways activated through this receptor in pancreatic and other tumor cells. These signaling proteins may be targeted by means known in the art to disrupt the downstream signaling pathway that catalyzes tumorigenesis, by the usage of antibodies, antisense, RNA interference, small molecule inhibitors and vaccines.

Immunogenic Polypeptides Encoded by MAGE Minigenes and Uses Thereof

The invention discloses immunogenic polypeptides comprising several MAGE-specific antigen epitopes selected from different (i.e. discrete) members of the MAGE protein family, nucleic acids coding therefor, recombinant viruses and/or cells comprising said nucleic acids, and compositions thereof. Methods for eliciting or inducing MAGE-specific immune responses utilizing the aforementioned immunogenic agents are also disclosed.

VIRAL CHEMOKINE-ANTIGEN FUSION PROTEINS

The present invention relates to a vaccine for increasing the immunogenicity of a tumor antigen thus allowing treatment of cancer, as well as a vaccine that increases the immunogenicity of a viral antigen, thus allowing treatment of viral infection, including immunodeficiency virus (HIV) infection. In particular, the present invention provides a fusion protein comprising a viral chemokine fused to either a tumor antigen or viral antigen which is administered as either a protein or nucleic acid vaccine to elicit an immune response effective in treating cancer or effective in treating or preventing viral infection. 1. A fusion polypeptide comprising a viral chemokine and a human tumor antigen , wherein the viral chemokine comprises viral macrophage inflammatory protein III (vMIPIII).2. The fusion polypeptide of claim 1 , wherein the human tumor antigen comprises a B cell tumor antigen.3. The fusion polypeptide of claim 2 , wherein the B cell tumor antigen is selected from the group consisting of:(1) an antibody produced by a B cell tumor;(2) a single chain antibody comprising linked VH and VL domains which retain the conformation and specific binding activity of the native idiotype of the antibody produced by a B cell tumor; and(3) an epitope of an idiotype of an antibody produced by a B cell tumor.4. The fusion polypeptide of claim 3 , wherein the B cell tumor antigen comprises sFv38.5. The fusion polypeptide of claim 1 , wherein the human tumor antigen comprises gp100.6. The fusion polypeptide of claim 1 , wherein the human tumor antigen comprises Muc-1.7. The fusion polypeptide of claim 1 , wherein the human tumor antigen comprises the amino acid sequence of SEQ ID NO: 1.8. A composition comprising the fusion polypeptide of in a pharmaceutically acceptable carrier.9. A method of producing an immune response in a subject claim 8 , comprising administering to the subject the composition of .10. The method of claim 9 , wherein the immune response is an effector T cell ...

Ttll4 peptides and vaccines containing the same

Peptide vaccines against cancer are described herein. In particular, epitope peptides derived from the TTLL4 gene that elicit CTLs are provided. Antigen-presenting cells and isolated CTLs that target such peptides, as well as methods for inducing the antigen-presenting cell, or CTL are also provided. The present invention further provides pharmaceutical compositions containing peptides derived from TTLL4 or polynucleotides encoding the polypeptides as active ingredients. Furthermore, the present invention provides methods for the treatment and/or prophylaxis of (i.e., preventing) cancers (tumors), and/or the prevention of a postoperative recurrence thereof, as well as methods for inducing CTLs, methods for inducing anti-tumor immunity, using the peptides derived from TTLL4, polynucleotides encoding the peptides, or antigen-presenting cells presenting the peptides, or the pharmaceutical compositions of the present invention.

Novel human ulip/crmp protein and use thereof in diagnosis and treatment of cancers and paraneoplastic neurological syndromes

A purified polypeptide, designated ULIP6, comprising the amino acid sequence SED ID No. 2 or an epitopic fragment of said polypeptide, comprising the sequence SEQ ID No. 4, is provided along with its nucleic acid sequences. In addition, antibodies to the polypeptide and methods of diagnosing paraneoplastic neurological syndromes and/or for the early diagnosis of the formation of cancerous tumors are also provided.

BISPECIFIC MOLECULE BINDING TLR9 AND CD32 AND COMPRISING A T CELL EPITOPE FOR TREATMENT OF ALLERGIES

A molecule or molecule complex capable of binding to TLR9 and to CD32 comprising at least one epitope of at least one antigen, and its use a medicament for the treatment of allergies. 1. A molecule or molecule complex comprising a TLR9 binding region capable of binding to TLR9 , a CD32 binding region capable of binding to CD32 , and at least one epitope of at least one antigen.2. A molecule or molecule complex according to claim 1 , characterized in that the epitope is a T cell epitope.3. A molecule or molecule complex according to claim 1 , characterized in that the epitope is derived from an allergen.4. A molecule or molecule complex according to claim 1 , characterized in that at least one epitope is non-covalently linked to the molecule or molecule complex.5. A molecule or molecule complex according to claim 1 , characterized in that at least one epitope is non-covalently linked to the TLR9 binding region or the CD32 binding region.6. A molecule or molecule complex according to claim 5 , characterized in that at least one epitope is linked to the TLR9 binding region or the CD32 binding region via ligand interaction.7. A molecule or molecule complex according to claim 1 , characterized in that the epitope is an epitope of an allergen selected from the group consisting of an allergen associated with atopic dermatitis claim 1 , an allergen associated with allergic asthma claim 1 , an allergen associated with allergic rhinitis or an allergen associated with allergic conjunctivitis.8. A molecule or molecule complex according to claim 1 , characterized in that the epitope is isolated from a source selected from the group consisting of complete antigens claim 1 , denatured antigens claim 1 , and antigens modified to prevent binding to IgE.9. A molecule or molecule complex according to claim 1 , characterized in that it comprises at least one antibody.10. A molecule or molecule complex according to claim 9 , characterized in that the antibody is selected from the group ...

GENETIC PRODUCTS DIFFERENTIALLY EXPRESSED IN TUMORS AND USE THEREOF

The invention relates to the identification of genetic products that are expressed in association with a tumor and the nucleic acid coding therefor. The invention relates to the therapy and diagnosis of diseases in which the genetic products that are expressed in association with a tumor are expressed in an aberrant manner. The invention also relates to proteins, polypeptides, and peptides which are expressed in association with a tumor and the nucleic acids coding therefor. 1117.-. (canceled)119. The pharmaceutical composition as claimed in claim 118 , in which the agent according to (I) or (II) is an antisense nucleic acid which hybridizes selectively with the nucleic acid coding for the tumor-associated antigen or is an antibody which binds selectively to the tumor-associated antigen.120. The pharmaceutical composition as claimed in claim 118 , in which the agent according to (III) comprises one or more components selected from the group consisting of:(i) the tumor-associated antigen or a part thereof,(ii) a nucleic acid which codes for the tumor-associated antigen or a part thereof,(iii) a host cell which expresses the tumor-associated antigen or a part thereof, and(iv) isolated complexes between the tumor-associated antigen or a part thereof and an HLA molecule.121. A pharmaceutical composition claim 118 , comprising one or more components selected from the group consisting of:(i) a tumor-associated antigen or a part thereof,(ii) a nucleic acid which codes for a tumor-associated antigen or a part thereof,(iii) an antibody which binds to a tumor-associated antigen or a part thereof,(iv) an antisense nucleic acid which hybridizes specifically with a nucleic acid coding for a tumor-associated antigen,(v) a host cell which expresses a tumor-associated antigen or a part thereof, and said tumor-associated antigen having a sequence encoded by a nucleic acid which is selected from the group consisting of:', '(a) a nucleic acid which comprises a nucleic acid sequence ...

COLON AND PANCREAS CANCER PEPTIDOMIMETICS

The invention relates to a peptidomimetic of an NPC-1 epitope on the MUC5AC protein which is differentially expressed in pancreatic and colorectal cancer, and diagnostic and therapeutic usages. Further, antibodies that selectively bind the NPC-1 epitope peptidomimetics and may be used in diagnostic and therapeutic methods. 1. An isolated polypeptide comprising a polypeptide at least about 80% identical to the amino acid sequence of SXPXDXFRYXNX(SEQ ID NO: 1) , wherein Xis for L; Xis E or D; Xis Y or W; Xis T or I and Xis Q or Y; SXPXDXFRYXNXK (SEQ ID NO: 2) , wherein Xis for L; Xis E or D; Xis Y or W; Xis T or I and Xis Q or Y; SLEPEXDWXFRYXNY (SEQ ID NO: 3) , wherein Xis E or D; Xis W or Y; and Xis T or I; FPEDYFRYTNQK (SEQ ID NO: 4); SLPDDWFRYINY (SEQ ID NO: 5); or any one of the amino acid sequences of SEQ ID NOs: 6-24.2. The isolated polypeptide of claim 1 , wherein said polypeptide is at least about 90% identical to the amino acid sequence of SXPXDXFRYXNX(SEQ ID NO: 1) claim 1 , wherein Xis for L; Xis E or D; Xis Y or W; Xis T or I and Xis Q or Y; SXPXDXFRYXNXK (SEQ ID NO: 2) claim 1 , wherein Xis for L; Xis E or D; Xis Y or W; Xis T or I and Xis Q or Y; SLEPEXDWXFRYXNY (SEQ ID NO: 3) claim 1 , wherein Xis E or D; Xis W or Y; and Xis T or I; FPEDYFRYTNQK (SEQ ID NO: 4); SLPDDWFRYINY (SEQ ID NO: 5); or any one of the amino acid sequences of SEQ ID NOs: 6-24.3. The isolated polypeptide of claim 1 , wherein said polypeptide comprises the amino acid sequence of SXPXDXFRYXNX(SEQ ID NO: 1) claim 1 , wherein Xis for L; Xis E or D; Xis Y or W; Xis T or I and Xis Q or Y; SXPXDXFRYXNXK (SEQ ID NO: 2) claim 1 , wherein Xis for L; Xis E or D; Xis Y or W; Xis T or I and Xis Q or Y; SLEPEXDWXFRYXNY (SEQ ID NO: 3) claim 1 , wherein Xis E or D; Xis W or Y; and Xis T or I; FPEDYFRYTNQK (SEQ ID NO: 4); SLPDDWFRYINY (SEQ ID NO: 5); or any one of the amino acid sequences of SEQ ID NOs: 6-24.43. A fusion protein comprising the polypeptide of any one of claim 1 , claim 1 , or .5. ...

Method for identifying immunoreactive peptides

The invention relates to a method for identifying immunoreactive peptides. According to said method, a sample of tumorous and corresponding healthy tissue is first provided, the tumor-specific expression profile is subsequently determined and antigenic peptides are isolated from the tumorous tissue and analyzed. The respective data that has been obtained is then matched and peptides are identified on the basis of said data.

Modified polynucleotides for the production of secreted proteins

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Tyrosine-phosphorylated wbp2, a novel cancer target and biomarker

WW-binding protein 2 (WBP2) has been demonstrated in different studies to be a tyrosine kinase substrate, to activate ERα/PR transcription and to play a role in breast cancer. However, the role of WBP2 tyrosine phosphorylation in regulating ER function and breast cancer biology is unknown. Here, we established WBP2 as a tyrosine phosphorylation target of estrogen signaling via EGFR crosstalk. Using dominant negative, constitutively active mutants, RNAi and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases. We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity putatively by blocking nuclear entry of WBP2 and its interaction with ERα. Compared to vector control, overexpression of WBP2 and its phospho-mimic mutant in MCF7 resulted in larger tumors in mice, induced loss of cell-cell adhesion, enhanced cell proliferation, anchorage-independent growth, migration and invasion in both estrogen-dependent and-independent manner, events of which could be substantially abolished by overexpression of phosphorylation-defective mutant. Wnt/β-catenin inhibitor FH535 blocked phospho-WBP2-mediated cancer cell growth more pronouncedly than tamoxifen and fulvestrant, in part by reducing the expression of ERα.

Oxidative stress responsive apoptosis inducing protein eif5a

Secreted eIF5A protein which is useful for diagnosis, prevention, and treatment of various diseases induced by an oxidative stress.

Inhibitors of Apoptosis and Uses Thereof

The invention relates to fragments of the DAXX and FADD proteins that inhibit cell apoptosis, in particular cell apoptosis mediated by the Fas receptor. The invention also relates to derivatives of said anti-apoptotic fragments, conjugates comprising said fragments, pharmaceutical compositions comprising said fragments, and to the medical applications of said fragments, derivatives, conjugates, and pharmaceutical compositions thereof in the treatment or prevention of diseases and conditions associated with apoptosis.

Muc18 targeting peptides

Provided are MUC18 targeting peptides which may be used, e.g., to therapeutically target B-1 lymphocytes to reduce the influence of these cells on the metastatic potential of melanoma cells and/or to target cancerous cells, including certain melanoma and leukemia cells. MUC18 targeting peptides may be comprised in fusion constructs, imaging constructs, and/or therapeutic constructs such as fusion constructs which may be used for diagnosing or treating a cancer.

Tumor targeted tnf-related apoptosis inducing ligand fusion polypeptide, methods and uses therefor

Fusion polypeptides comprising a TRAIL trimer and a targeting domain are disclosed. The targeting domain can be, in some embodiments, a sequence that binds MUC16, which is prevalent on some tumor cells such as pancreatic and ovarian tumor cells. A sequence that binds MUC 16 can be mesothelin or a MUC16-binding fragment thereof, such as amino acids 1-64 of mesothelin. A fusion polypeptide of the present teachings can induce apoptosis in a target cell such as a MUC16-expressing cancer cell. Also disclosed are nucleic acids encoding the fusion polypeptides, and methods of use of the fusion polypeptides and nucleic acids.

WDRPUH Epitope Peptides and Vaccines Containing the Same

The present invention provides peptides containing the amino acid sequence of SEQ ID NOs: 1, 2, 3, 4, 16, 17, 30, 31, 34, 36, 37, 40, 41, 45, 49, 55, 57 and 61, as well as peptides containing the above-mentioned amino acid sequences in which 1, 2, or several amino acid(s) are substituted, deleted, inserted or added, but still have cytotoxic T cell inducibility. The present invention also provides drugs for treating or preventing tumors, which drugs containing these peptides. The peptides of the present invention can also be used as vaccines. 1. An isolated peptide of less than 15 amino acids selected from the group consisting of:(a) an isolated peptide, which comprises the amino acid sequence as shown in SEQ ID NO: 34; and(b) an isolated peptide, which comprises the amino acid sequence as shown in SEQ ID NO: 34 in which 1, 2, or several amino acid(s) are substituted, deleted, inserted and/or added, wherein the added amino acid(s) are added to the N-terminus and/or C-terminus.2. The peptide of claim 1 , wherein the peptide has one or both of the following characteristics:(a) the second amino acid from the N-terminus is selected from the group consisting of leucine and methionine; and(b) the C-terminal amino acid is selected from the group consisting of valine and leucine.3. An agent for inducing CTL claim 1 , wherein the agent contains one or more peptide(s) of .4. A pharmaceutical agent for the treatment and/or prophylaxis of cancers claim 1 , and/or the prevention of postoperative recurrence thereof claim 1 , wherein the agent comprises one or more peptide(s) of .5. The pharmaceutical agent of claim 4 , formulated for the administration to a subject whose HLA antigen is HLA-A2.6. A method for inducing an antigen-presenting cell (APC) with CTL inducibility claim 4 , wherein the method comprises the step selected from:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) contacting an APC with the peptide of in vitro, ex vivo or in vivo; and'}{'claim-ref': {'@idref ...

HIGHLY POTENT PEPTIDES TO CONTROL CANCER AND NEURODEGENERATIVE DISEASES

This invention provides compositions and method of diminishing or inhibiting autophagy by administering a FLIP protein that binds to Atg3, interfering with the formation of the LC3-Atg4-Atg7-Atg3 conjugation complex necessary for autophagy induction. This invention also provides FLIP peptide fragments that promote or induce autophagy by interfering with the activity of FLIP. 1. A method for increasing or inducing the death of a cancer cell comprising administering to the cell an effective amount of one or more of: a FLIP peptide fragment , variant , hybrid or biological equivalent thereof , an amino acid comprising SEQ ID. NOS. 1 through 8 , 15 through 18 , 41 through 47 or a biological equivalent of each thereof , a FLIP peptide fragment isolated from a FLIP protein death effector domain region of the FLIP protein or from a portion of the death effector domain region of the FLIP protein , a FLIP peptide fragment isolated from an alpha-helix fragment of the FLIP protein death effector domain region or from a portion of the alpha-helix fragment of the FLIP protein death effector domain region , or a peptide selected from one or more of:(a) an isolated or recombinant peptide comprising one or more peptide shown in SEQ ID NO. 41 through 47, or an amino acid sequence having at least 80% homology to an amino acid sequence of SEQ ID NO. 41 to 47, wherein amino acid 5 and/or 6 is Lor W, respectively;(b) an isolated or recombinant variant peptide comprising an amino acid sequence selected from SEQ ID NOS. 2, 4, 6 or 8, having a substitution with 1, 2, 3, or 4 amino acids at the corresponding positions of the a region of one or more other peptides selected from SEQ ID NOS. 2, 4, 6 or 8;(c) an isolated or recombinant peptide comprising a hybrid peptide between any two amino acid sequences selected from SEQ ID NO.2, 4, 6 or 8 or a peptide having at least 80% homology to the hybrid peptide;(d) an isolated or recombinant hybrid peptide comprising anN-terminal amino acid sequence ...

BLID; a novel protein domain for interaction with the Bcl-2 family of proteins

In this invention, a novel protein interaction domain is provided along with several of its variants. This domain is involved in protein-protein interactions with the Bcl-2 family of proteins. It is named BLID (Bcl2 family of proteins Like Interaction Domain). Use of BLID and its variants for modulating cellular activity is presented. BLID, its variants and or anti-BLID antibodies could be useful as a screening tool as well as for discovery of drugs that help fight pathological states like degenerative diseases, cerebral or cardiac ischemic hypoxic disorders, cancer and autoimmunity. 1- A polypeptide comprising a novel protein interacting domain capable of protein-protein interactions with members of the Bcl-2 family of proteins , wherein the amino acid sequence of said protein interacting domain comprises at least 6 contiguous amino acids from at least one of the following individual sequences: SEQ ID NO 01-24.2- An isolated nucleic acid (polynucleotide) that encodes for polypeptide of claim 1 , wherein the nucleotide sequence of said isolated nucleic acid comprises at least 18 contiguous nucleotides from SEQ ID 26 or SEQ ID 27.3- The polypeptide of claim 1 , wherein said polypeptide functions as an anti-apoptotic factor.4- A chimeric polypeptide comprising a polypeptide moiety and the polypeptide of claim 1 , wherein the polypeptide moiety is genetically engineered at the N-terminal or C-terminal end of the polypeptide and the polypeptide moiety comprises a molecule selected from the group of: fluorescent proteins (GFP claim 1 , EGFP claim 1 , RFP claim 1 , etc) claim 1 , GST (Glutathione-S-Transferase) claim 1 , MBP (Maltose Binding Protein) claim 1 , Beta-galactosidase claim 1 , Inteins claim 1 , Streptavidin claim 1 , His-tag claim 1 , Myc-epitope claim 1 , HA-Tag claim 1 , and FLAG.5- A chimeric polypeptide comprising polypeptide moiety consisting of a cell penetrating peptide (CPP) like Tat-HIV genetically engineered at the N-terminal or C-terminal end of the ...

Identification of Tumor-Associated Antigens for Diagnosis and Therapy

The invention relates to genetic products the expression of which is associated with cancer diseases. The invention also relates to the therapy and diagnosis of diseases in which the genetic products are expressed or aberrantly expressed, in particular cancer diseases. 16.-. (canceled)7. A pharmaceutical composition , comprising one or more components selected from the group consisting of:(i) a tumor-associated antigen or a part thereof,(ii) a nucleic acid which codes for a tumor-associated antigen or a part thereof,(iii) an antibody which binds to a tumor-associated antigen or a part thereof,(iv) an antisense nucleic acid which hybridizes specifically with a nucleic acid coding for a tumor-associated antigen,(v) an siRNA directed against a nucleic acid coding for a tumor-associated antigen,(vi) a host cell which expresses a tumor-associated antigen or a part thereof, and (a) a nucleic acid which comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 5, 1, 9, 13, 17, 21, 25, 28, 30, 35, 39, 41, 45, 49, 61, 62, and 64-67, a part or derivative thereof,', '(b) a nucleic acid which hybridizes with the nucleic acid of (a) under stringent conditions,', '(c) a nucleic acid which is degenerate with respect to the nucleic acid of (a) or (b), and', '(d) a nucleic acid which is complementary to the nucleic acid of (a), (b) or (c)., '(vii) isolated complexes between a tumor-associated antigen or a part thereof and an MHC molecule, said tumor-associated antigen having a sequence encoded by a nucleic acid which is selected from the group consisting of8. (canceled)9. (canceled)10. The pharmaceutical composition as claimed in claim 7 , in which the host cell additionally expresses an MHC molecule which binds to the tumor-associated antigen or the part thereof.11. (canceled)12. (canceled)13. The pharmaceutical composition as claimed in claim 7 , in which the host cell is an antigen-presenting cell.14. The pharmaceutical composition as claimed in claim 7 ...

VACCINES DIRECTED TO LANGERHANS CELLS

The present invention includes isolated anti-Langerin vaccines, methods for making and using an isolated anti-Langerin antibody or binding fragment thereof and one or more antigenic peptides at the carboxy-terminus of the isolated anti-Langerin antibody, wherein when two or more antigenic peptides are present, the peptides are separated by the one or more linker peptides that comprise at least one glycosylation site. The present invention also includes isolated vectors for the expression of the anti-Langerin antigen delivery vectors and their manufactures and use. 1. A vaccine comprising an isolated anti-Langerin antibody or binding fragment thereof and one or more antigenic peptides at the carboxy-terminus of the anti-Langerin antibody , wherein when two or more antigens are present , they are separated by one or more linker peptides that comprise at least one glycosylation site.218-. (canceled)19. A method of enhancing T and B cell responses comprising:immunizing a subject in need of vaccination with an effective amount of a vaccine comprising an isolated fusion protein comprising an anti-Langerin antibody or binding portion thereof and one or more antigenic peptides linked to the carboxy-terminus of the anti-Langerin antibody.20. The method of claim 19 , wherein the antigenic peptides are cancer peptides selected from tumor associated antigens selected from CEA claim 19 , prostate specific antigen (PSA) claim 19 , HER-2/neu claim 19 , BAGE claim 19 , GAGE claim 19 , MAGE 1-4 claim 19 , 6 and 12 claim 19 , MUC (Mucin) (e.g. claim 19 , MUC-1 claim 19 , MUC-2 claim 19 , etc.) claim 19 , GM2 and GD2 gangliosides claim 19 , ras claim 19 , myc claim 19 , tyrosinase claim 19 , MART (melanoma antigen) claim 19 , MARCO-MART claim 19 , cyclin B1 claim 19 , cyclin D claim 19 , Pmel 17 (gp100) claim 19 , GnT-V intron V sequence (N-acetylglucoaminyltransferase V intron V sequence) claim 19 , Prostate Ca psm claim 19 , prostate serum antigen (PSA) claim 19 , PRAME (melanoma ...

T-cell death-inducing epitopes

Cell death-inducing epitopes and polypeptides containing same. Also disclosed are compounds for inducing death of activated T-cells, a method of producing antibodies to the epitopes, a method of identifying compounds that bind to the epitopes, a method of inducing death of activated T-cells, and pharmaceutical compositions containing the compounds.

PEPTIDES AND METHODS FOR INDUCING CELL DEATH

The invention provide isolated peptides, protides and conjugates having novel peptide sequences which are able to induce antimicrobial, anti-cancer, anti-inflammatory, anti-proliferative or programmed cell death activity. The invention also provides a method of inducing programmed cell death in a cell by contacting the cell with an isolated peptide, protide or conjugate described herein. In some aspects, the method can be used in the diagnosis, prevention, or treatment of a disease, such as an infection, cancer, autoimmune disease, or inflammatory disease. 1. An isolated peptide comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 17 , 18 , 19 , 21-25 , 30 , 31-36 , 39-47 , 49-52 , 54-57 , 59-63 , 66-75 , 84-93 , 102-106 , 108-121 , 132-175 , 179-187 , 191-199 , 205-209 , 211-223 , 227-235 , 238-243 , 245-247 , 249-251 , 253-256 and 260-263 , wherein the amino acid residue represented by (x) is a serine , a threonine , a tryptophan , a H-bond donor residue or a H-bond acceptor residue , wherein the amino acid residue represented by (b) is a lysine , an arginine , an asparagine , a glutamine or a basic residue , wherein the amino acid residue represented by (j) is a cysteine or a thiol residue , wherein in the amino acid residue represented by (o) is an anthrylalanine or other non-natural amino acid and wherein said peptide induces antimicrobial , anti-cancer , anti-inflammatory , anti-proliferative or programmed cell death activity.2170-. (canceled)171. The isolated peptide of comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 17 claim 1 , 18 claim 1 , 19 claim 1 , 21-25 claim 1 , 269 and 272.172. The isolated peptide of comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 30 claim 1 , 31-36 and 273.173. The isolated peptide of comprising one or more amino acid sequence selected from the group consisting of SEQ ID NOS: 39-47.174. The isolated ...

Autophagy-Inducing Peptide

An autophagy-inducing compound comprises an autophagy-inducing peptide comprising beclin-1 residues 269-283 and a heterologous moiety that promotes therapeutic stability or delivery of the compound. The compound may be used to induce autophagy and in assays with beclin-1 binding partners.

MULTIMODAL TRAIL MOLECULES AND USES IN CELLULAR THERAPIES

Described herein are novel compositions comprising multimodal TRAIL agents and cells engineered to express such multimodal TRAIL agents, including cells encapsulated in a scaffold or matrix, for use in the treatment of disorders such as cancer. 1. A multimodal TRAIL agent comprising a reporter module and a therapeutic TRAIL module , wherein said therapeutic TRAIL module comprises an extracellular domain of human TRAIL.2. The multimodal TRAIL agent of claim 1 , wherein the extracellular domain of human TRAIL comprises amino acids 114-281 of SEQ ID NO: 1.3. The multimodal TRAIL agent of claim 1 , further comprising a signal sequence.4. The multimodal TRAIL agent of claim 3 , wherein the signal sequence comprises SEQ ID NO: 2.5. The multimodal TRAIL agent of claim 1 , wherein the therapeutic TRAIL module further comprises an isoleucine zipper domain.6. The multimodal TRAIL agent of claim 1 , further comprising a linker domain C-terminal to the reporter module and N-terminal to the therapeutic TRAIL module.7. The multimodal TRAIL agent of claim 6 , wherein the linker domain comprises at least eight amino acids.8. The multimodal TRAIL agent of claim 6 , wherein the linker domain comprises the amino acid sequence of SEQ ID NO: 4.9. A pharmaceutical composition comprising the multimodal TRAIL agent of and a pharmaceutically acceptable carrier.10. (canceled)11. (canceled)12. A cell comprising the nucleic acid sequence encoding a multimodal TRAIL agent comprising a reporter module and a therapeutic TRAIL module claim 1 , wherein said therapeutic TRAIL module comprises an extracellular domain of human TRAIL.13. (canceled)14. The cell of claim 12 , wherein the cell is a stem cell.15. (canceled)16. The cell of claim 12 , wherein the cell is encapsulated in a matrix or scaffold.1729.-. (canceled)30. A method of treating a subject having a malignant condition comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a multimodal TRAIL ...

COMPOUNDS THAT INHIBIT HSP90 PROTEIN-PROTEIN INTERACTIONS WITH IAP PROTEINS

Disclosed herein are compounds that inhibit Hsp90 interactions with IAP proteins, such as Survivin, XIAP, cIAP1, or cIAP2, and methods for identifying and using such compounds. 116.-. (canceled)17. A method of treating a cancer associated with overexpression of Survivin in a subject , the method comprising:selecting a subject diagnosed as having a cancer associated with overexpression of Survivin; andadministering to the selected subject a therapeutically effective amount of a pharmaceutical composition comprising a compound:(i) consisting of a D-amino acid peptide selected from the group consisting of: (D-Leu)-(D-Phe)-(D-Ala)-(D-Cys)-(D-Gly)-(D-Ser)-(D-Ser)-(D-His)-(D-Lys); (D-Cys)-(D-Gly)-(D-Ser)-(D-Ser)-(D-His); and (D-Gly)-(D-Ser)-(D-Ser)-(D-His)-(D-Lys); or(ii) comprising the formula X-A or A-X, wherein A consists of a D-amino acid sequence selected from the group consisting of: (D-Leu)-(D-Phe)-(D-Ala)-(D-Cys)-(D-Gly)-(D-Ser)-(D-Ser)-(D-His)-(D-Lys); (D-Cys)-(D-Gly)-(D-Ser)-(D-Ser)-(D-His); and (D-Gly)-(D-Ser)-(D-Ser)-(D-His)-(D-Lys); and X consists of an internalization peptide sequence of a protein selected from the group consisting of: Tat, Antennapedia, VP22, Pep-1, and transportan, or a retro-inverso version of said internalization peptide sequence.1829-. (canceled)30. The method of claim 17 , wherein the compound comprises the formula X-A or A-X claim 17 , wherein:A consists of a D-amino acid sequence selected from the group consisting of: (D-Leu)-(D-Phe)-(D-Ala)-(D-Cys)-(D-Gly)-(D-Ser)-(D-Ser)-(D-His)-(D-Lys); (D-Cys)-(D-Gly)-(D-Ser)-(D-Ser)-(D-His); and (D-Gly)-(D-Ser)-(D-Ser)-(D-His)-(D-Lys); andX consists of an internalization peptide sequence of a protein selected from the group consisting of: Tat, Antennapedia, VP22, Pep-1, and transportan, or a retro-inverso version of said internalization peptide sequence.31. The method of claim 30 , wherein the compound comprises a D-amino acid sequence selected from:(D-Lys)-(D-Lys)-(D-Trp)-(D-Lys)-(D-Met)-(D-Arg ...

INDUCTION AND ENHANCEMENT OF ANTITUMOR IMMUNITY INVOLVING SINDBIS VIRUS VECTORS EXPRESSING IMMUNE CHECKPOINT PROTEINS

Provided are polynucleotides and viral vectors, particularly, vectors such as Sindbis viral vectors, which encode an immune checkpoint protein, or a ligand binding portion of the checkpoint protein, or an immune checkpoint protein or ligand binding portion thereof fused to one or more immunoglobulin (Ig) domains, e.g., an Ig hinge region and an Ig heavy chain constant domain. Methods of treating a mammalian subject having a cancer or tumor are provided, in which the viral vectors, e.g., a Sindbis virus vector, encoding the immune checkpoint protein, a ligand binding portion thereof, or a checkpoint protein fusion protein as described, are administered to the subject, resulting in an anti-cancer or anti-tumor immune response, significant reduction in tumor growth in the treated subject and increased survivability. 1. A therapeutic composition comprising a Sindbis virus encoding an immune checkpoint protein or a cognate ligand binding portion thereof.2. The therapeutic composition of claim 1 , wherein the immune checkpoint protein or the cognate ligand binding portion thereof is fused to an immunoglobulin hinge region and an immunoglobulin heavy chain constant domain.3. The therapeutic composition of claim 2 , wherein the Sindbis virus encoding a fusion polypeptide comprises a secretory signal sequence linked to the immunoglobulin heavy chain constant domain claim 2 , which is linked to the immune checkpoint protein claim 2 , or an extracellular domain thereof; and wherein the fusion protein comprises one or more linker sequences.4. The therapeutic composition of claim 2 , wherein the fusion protein comprises a linker sequence between the hinge region and the immunoglobulin heavy chain constant domain.5. The therapeutic composition of claim 2 , wherein the immunoglobulin is IgG claim 2 , IgG1 claim 2 , or IgG2a.6. The therapeutic composition of claim 5 , wherein the heavy chain constant domain is the CH3 domain.7. The therapeutic composition of claim 3 , wherein the ...

Novel peptides and scaffolds for use in immunotherapy against head and neck squamous cell carcinoma and other cancers

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of treating cancer in a HLA-A*02+ patient , wherein said cancer comprises cancer cells that overexpress KRT5 and present at their surface in complex with an MHC class I molecule a peptide consisting of the amino acid sequence STASAITPSV (SEQ ID NO: 9) , said method comprising administering to said patient an effective amount of activated antigen-specific CD8+ cytotoxic T cells to kill the cancer cells , wherein said activated antigen-specific CD8+ cytotoxic T cells are produced by contacting in vitro CD8+ cytotoxic T cells with an antigen presenting cell presenting at its surface in complex with an MHC class I molecule a peptide consisting of the amino acid sequence STASAITPSV (SEQ ID NO: 9) , wherein said cancer is selected from head and neck cancer , non-small cell lung cancer (NSCLC) , small cell lung cancer (SCLC) , renal cell carcinoma (RCC) , brain cancer , gastric cancer (GC) , chronic lymphatic leukemia (CLL) , non-Hodgkin lymphoma (NHL) , ovarian cancer (OC) , breast cancer (BRCA) , esophageal cancer , gallbladder cancer , bile duct cancer , urinary bladder cancer , and liver cancer (HCC).2. The method of claim 1 , wherein the cytotoxic T cells produced by contacting CD8+ cytotoxic T cells with said antigen presenting cell are cytotoxic T ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST EPITHELIAL OVARIAN CANCER AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of eliciting an immune response in a patient who has cancer , comprising administering to said patient a composition comprising a population of activated T cells that kill cancer cells in the patient that present a peptide , wherein said peptide consists of the amino acid sequence of SEQ ID NO: 130 , 1 , 122 , 128 , 2 , 86 , 98 , 119 , 147 , 3-81 , 83 , 85 , 87-97 , 99-118 , 120 , 121 , 123-127 , 129 , 131-146 , or 148-549 , wherein said cancer is selected from the group consisting of ovarian cancer , non-small cell lung cancer , small cell lung cancer , kidney cancer , brain cancer , colon or rectum cancer , stomach cancer , liver cancer , pancreatic cancer , prostate cancer , leukemia , breast cancer , Merkel cell carcinoma , melanoma , esophageal cancer , urinary bladder cancer , uterine cancer , gallbladder cancer , and bile duct cancer.2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the T cells are derived from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.5. The method of claim 1 , further comprising expanding T cells in vitro.6. The method of claim 1 , wherein the peptide is in ...

Novel peptides and combination of peptides for use in immunotherapy against epithelial ovarian cancer and other cancers

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

CONDITIONAL SUPERAGONIST CTL LIGANDS FOR THE PROMOTION OF TUMOR-SPECIFIC CTL RESPONSES

What is described is a method of treatment of a patient with a tumor, comprising administering a cell responsive to a peptide comprising a tumor epitope, wherein the tumor epitope comprises an amino acid substitution in a tumor antigen. The tumor antigen is preferably selected from the group consisting of NYESO-I, NYESO-II, or MART-1, preferably SEQ ID NOS: 1-351, 361-376, and 392-401. 1. A method of treatment of a patient with a tumor , comprising administering a cell responsive to a peptide comprising a tumor epitope , wherein the tumor epitope comprises an amino acid substitution in a tumor antigen , and wherein the tumor antigen is selected from the group consisting of SEQ ID NOS: 1-351 , 361-376 , and 392-401.2. The method of claim 1 , wherein the tumor epitope comprises an amino acid substitution in a tumor antigen claim 1 , wherein the tumor antigen is SEQ ID NO: 144 or 228 claim 1 , and wherein the tumor epitope comprises a sequence selected from the group consisting of SEQ ID NOS: 362-365 and 368-376.3. The method of claim 2 , wherein the tumor antigen is SEQ ID NO: 144 claim 2 , and wherein the tumor epitope comprises a sequence selected from the group consisting of SEQ ID NOS: 368-376.4. The method of claim 3 , wherein the tumor epitope comprises a sequence consisting of SEQ ID NOS: 372 claim 3 , 374 claim 3 , or 375.5. The method of claim 2 , wherein the tumor antigen is SEQ ID NO: 228 claim 2 , and the tumor epitope comprises a sequence selected from the group consisting of SEQ ID NOS: 362-365.6. The method of claim 5 , wherein the tumor antigen is SEQ ID NO: 228 claim 5 , and the tumor epitope comprises a sequence selected from the group consisting of SEQ ID NOS: 362 claim 5 , 363 or 365.7. The method of claim 1 , wherein the tumor epitope comprises a multiplicity of sequences selected from the group consisting of SEQ ID NOS: 362-365 and 368-376.8. The method of claim 7 , wherein the tumor epitope comprises a multiplicity of sequences selected from the ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST PROSTATE CANCER AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of eliciting an immune response in a patient who has cancer , comprising administering to said patient a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence selected from SEQ ID NO: 24 , wherein said cancer is selected from liver cancer , benign prostate hyperplasia , and prostate cancer.2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.5. The method of claim 1 , wherein the activated T cells are expanded in vitro.6. The method of claim 1 , wherein the population of activated T cells are administered in the form of a composition.7. The method of claim 6 , wherein the composition further comprises an adjuvant.8. The method of claim 7 , wherein the adjuvant is selected from anti-CD40 antibody claim 7 , imiquimod claim 7 , resiquimod claim 7 , GM-CSF claim 7 , cyclophosphamide claim 7 , sunitinib claim 7 , bevacizumab claim 7 , interferon-alpha claim 7 , interferon-beta claim 7 , CpG oligonucleotides and derivatives claim 7 , poly-(I:C) and derivatives ...

Virus Vectors Expressing Multiple Epitopes of Tumor Associated Antigens For Inducing Antitumor Immunity

Provided are polynucleotides and viral vectors, particularly, alphavirus vectors such as Sindbis viral vectors, which encode multiple, e.g., two or more, epitopes of at least one tumor associated antigen in which each epitope is separated by a processing or enzyme cleavage site. The multiple epitopes of the two or more tumor associated antigens encoded by the described polynucleotides and viral vectors may be the same or different. Methods of treating mammalian subjects having a cancer or tumor expressing the tumor associated antigen epitopes are provided, in which the viral vectors encoding the multiple epitopes, as well as other immunostimulatory or immunomodulatory components, generate an anti-cancer or anti-tumor immune response in which high levels of effector T cells increase the survivability of tumored mammalian subjects and result in epitope spreading, thus providing a further enhancement of the immune response. 1. A polynucleotide encoding an alphavirus protein , or a fragment thereof , and two or more epitopes of one or more tumor associated antigens , wherein each epitope is separated by an enzyme cleavage site.2. The polynucleotide of claim 1 , wherein the alphavirus protein claim 1 , or a fragment thereof claim 1 , is a Sindbis virus protein claim 1 , or a fragment thereof.3. The polynucleotide of claim 1 , wherein the two or more epitopes comprise an amino acid sequence of a tumor associated antigen listed in any one of Tables 1-28.4. The polynucleotide of claim 3 , wherein the two or more epitopes are of one or more tumor associated antigens selected from kallikrein 4 claim 3 , papillomavirus binding factor (PBF) claim 3 , preferentially expressed antigen of melanoma (PRAME) claim 3 , Wilms' tumor-1 (WT1) claim 3 , Hydroxysteroid Dehydrogenase Like 1 (HSDL1) claim 3 , mesothelin claim 3 , cancer testis antigen (NY-ESO-1) claim 3 , carcinoembryonic antigen (CEA) claim 3 , p53 claim 3 , human epidermal growth factor receptor 2/neuro receptor tyrosine ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST VARIOUS CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of treating a patient who has cancer , comprising administering to the patient an effective amount of an antibody specifically binding to an MHC class I or II molecule complexed with an antigen consisting of the amino acid sequence of VQLDSIEDLEV (SEQ ID NO: 32) ,wherein said cancer is selected from the group consisting of glioblastoma, breast cancer, colorectal cancer, renal cell carcinoma, chronic lymphocytic leukemia, hepatocellular carcinoma, non-small cell lung cancer, small cell lung cancer, Non-Hodgkin lymphoma, acute myeloid leukemia, ovarian cancer, pancreatic cancer, prostate cancer, esophageal cancer, gallbladder cancer and cholangiocarcinoma, melanoma, gastric cancer, urinary bladder cancer, head- and neck squamous cell carcinoma, and uterine cancer.2. The method of claim 1 , wherein the antibody is a polyclonal antibody claim 1 , a monoclonal antibody claim 1 , a bi-specific antibody claim 1 , or a chimeric antibody.3. The method of claim 1 , wherein the antibody binds to the HLA-restricted antigen with a binding affinity of below 20 nanomolar.4. The method of claim 1 , wherein the antibody binds to the MHC class I molecule complexed with the HLA-restricted antigen.5. The method of claim 1 , wherein the antibody is humanized.6. The ...

DENDRITIC CELL COMPOSITION

The present invention contemplates dendritic cell compositions. The dentritic cell compositions employ MHC class-II targeting signals fused to an antigen or fragment thereof to obtain MHC II presentation of the antigen or fragment thereof. In particular, the invention refers to a dendritic cell vaccine comprising dendritic cells expressing a MHC class-II targeting signal fused to an antigen or fragment thereof. Dendritic cell vaccines for the stimulation of an immune response against melanoma-associated antigen are also described. 1. Dendritic cell composition comprising dendritic cells expressing at least one fusion protein comprisingat least one antigen or a fragment thereof,an endoplasmatic reticulum (ER)-translocation signal sequence preceding the N-terminus of the antigen, anda transmembrane and cytoplasmic domain comprising an endosomal/lysosomal targeting sequence following the C-terminus of the antigen.2. Dendritic cell composition according to claim 1 ,wherein the dendritic cell composition further comprises dendritic cells expressing at least one antigen or a fragment thereof wherein the antigen is not fused to a targeting signal sequences that promotes the MHC II presentation of the antigen or fragment thereof.3. Dendritic cell composition according to or claim 1 , wherein the targeting signal sequence that promotes the MHC II presentation is at least one selected from the group consisting ofan endoplasmatic reticulum (ER)-translocation signal sequence preceding the N-terminus of the antigen, anda transmembrane and cytoplasmic domain comprising an endosomal/lysosomal targeting sequence following the C-terminus of the antigen.4. Dendritic cell composition according to any one of the preceding claims claim 1 , wherein the fusion protein and the antigen are transiently or stably expressed claim 1 , preferably stably expressed.5. Dendritic cell composition according to claim 4 , wherein the transient expression is carried out by introducing ivt-RNA.6. ...

EPHA2 T-CELL EPITOPE AGONISTS AND USES THEREFORE

EphA2 T-cell epitope are provided herein. The epitopes include peptides corresponding to specific fragments of human EphA2 protein containing one or more T-cell epitopes, and conservative derivatives thereof. The EphA2 T-cell epitopis are useful in an assay, such as an ELISPOT assay, that may be used to determine and/or quantify a patient's immune responsiveness to EphA2. The epitopes also are useful in methods of modulating a patient's immune reactivity to EphA2, which has substantial utility as a treatment for cancers that overexpress EphA2, such as renal cell carcinoma (RCC). The EphA2 epitopes also can be used to vaccinate a patient against EphA2, by in vivo or ex vivo methods. 159-. (canceled)60. An isolated peptide that (i) consists of 9-35 amino acid residues , wherein said isolated peptide comprises a peptide TLADFDPRV (SEQ ID NO:2 , residues 883-891) having one conservative amino acid substitution within the conservative substitution groups (a) S and T , (b) L , I and V , and (c) E and D; and (ii) retains the ability to stimulate a T-cell immune response to EphA2 as determined by ELISPOT assay.61. The isolated peptide of further comprising a second peptide where said second peptide is not an EphA2 peptide and is immunogenic.62. A vaccine formulation comprising an isolated peptide that (i) consists of 9-35 amino acid residues claim 60 , wherein said isolated peptide comprises a peptide TLADFDPRV (SEQ ID NO:2 claim 60 , residues 883-891) having one conservative amino acid substitution within the conservative substitution groups (a) S and T claim 60 , (h) L claim 60 , I and V claim 60 , and (c) E and D; and (ii) retains the ability to stimulate a T-cell immune response to EphA2 as determined by ELISPOT assay claim 60 , and a pharmaceutically acceptable carrier.63. The vaccine formulation of that further comprises an adjuvant.64. The vaccine formulation of wherein the isolated peptide further comprises a second peptide where said second peptide is not an EphA2 ...

NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS OF THE BLOOD, IN PARTICULAR CHRONIC LYMPHOID LEUKEMIA (CLL)

The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to several novel peptide sequences and their variants derived from HLA class I and HLA class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses. 1. A method of eliciting an immune response in a patient who has cancer , comprising administering to said patient a population of activated T cells that selectively recognize cells , which present a peptide consisting of the amino acid sequence selected from the group consisting of from SEQ ID NO: 2 to SEQ ID NO: 76 and from SEQ ID NO: 78 to SEQ ID NO: 1016 , wherein said cancer is selected from the group consisting of chronic lymphoid leukemia (CLL) , acute myelogenous leukemia (AML) , adrenal gland adrenal cortical adenoma , bone giant cell tumor of bone , bone non-ossifying fibroma , breast carcinoma , colon adenocarcinoma , non-Hodgkin's lymphoma , endometrium adenocarcinoma endometrioid , kidney angiomyolipoma , kidney carcinoma , kidney oncocytoma , liver focal nodular hyperplasia , liver hepatocellular carcinoma , lymph node Hodgkin's disease , lymph node papillary carcinoma of thyroid , medullary carcinoma of thyroid origin , metastatic adenocarcinoma of stomach , neurofibroma , ovary thecoma fibroma , pancreas adenocarcinoma , pancreas microcystic adenoma , parathyroid gland adenoma , rectum adenocarcinoma , skin squamous cell carcinoma , spleen chronic myeloid leukemia , stomach gastrointestinal stromal tumor (GIST) , thyroid gland nodular hyperplasia , thyroid ...

HDM-2 TARGETING COMPOSITIONS CAUSE TUMOR CELL NECROSIS RATHER THAN APOPTOSIS OF CANCER CELLS

An aspect of the invention provides a method of selectively necrosing cells, comprising: providing a plurality cells, including at least one cancer cell and at least one non-cancerous cell; and administering to the cells a compound, including an HDM-2 targeting component and a cytotoxic component attached to the HDM-2 targeting component, wherein said compound comprises a membrane-active form. 1. A method of selectively necrosing cells , comprising:providing a plurality cells, including at least one cancer cell and at least one non-cancerous cell;administering to the cells a compound, including an HDM-2 targeting component and a cytotoxic component, said cytotoxic component attached to said HDM-2 targeting component, wherein said compound comprises a membrane-active form.2. The method of claim 1 , wherein the cytotoxic component is selected from the group consisting of: a membrane resident peptide claim 1 , a toxin claim 1 , a drug claim 1 , a radionuclide claim 1 , a whole antibody claim 1 , an antibody fragment claim 1 , and combinations thereof.3. The method of claim 1 , wherein the HDM-2 targeting component is selected from the group consisting of: a small molecule claim 1 , a peptide claim 1 , a protein claim 1 , a glycoprotein claim 1 , a whole antibody claim 1 , an antibody fragment claim 1 , and combinations thereof.4. The method of claim 1 , further comprising the step of observing in a cell medium a level of LDH.5. The method of claim 1 , further comprising the step of observing necrosis in the cancer cells.6. The method of claim 1 , further comprising the step of observing a non-response in the non-cancerous cell claim 1 , wherein the non-response indicates the non-cancerous cell is unaffected.7. The method of claim 1 , wherein the administering step further comprises administering a PNC-27 claim 1 , a PNC-28 peptide claim 1 , or combinations thereof.8. A method of causing membranolysis in at least one cancer cell claim 1 , comprising:administering to at ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES AND SCAFFOLDS THEREOF FOR USE IN IMMUNOTHERAPY AGAINST COLORECTAL CARCINOMA (CRC) AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T-cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. An expression vector expressing a nucleic acid encoding a peptide consisting of the amino acid sequence of KQFEGTVEI (SEQ ID NO: 138) or ALAAARVEL (SEQ ID NO: 17).2. A recombinant host cell comprising the peptide according to .3. A recombinant host cell comprising the nucleic acid according to .4. A recombinant host cell presenting HLA-A*02 on its surface comprising the expression vector according to claim 1 , wherein said host cell is optionally an antigen presenting cell.5. A method for producing a peptide consisting of the amino acid sequence of KQFEGTVEI (SEQ ID NO: 138) or ALAAARVEL (SEQ ID NO: 17) claim 3 , comprising culturing the host cell according to claim 3 , and isolating the peptide from the host cell or its culture medium.6. An in vitro method for producing activated T lymphocytes claim 3 , comprising contacting in vitro T cells with antigen loaded human HLA-A*0201 expressed on the surface of a suitable antigen-presenting cell or an artificial construct mimicking an antigen-presenting cell for a period of time sufficient to activate said T cells in an antigen specific manner claim 3 , wherein said antigen is a peptide consisting of the amino acid sequence of KQFEGTVEI (SEQ ID NO: 138) or ALAAARVEL (SEQ ID NO: 17).7. A method of treating a HLA-A* ...

GLYPICAN EPITOPES AND USES THEREOF

The present invention relates to epitopes of glypican-1 (GPC-1) and uses thereof. 151-. (canceled)52. An isolated epitope or epitope segment for an anti-glypican 1 (GPC-1) antibody located within a portion of the GPC-1 flexible loop defined by an amino acid sequence KVNPQGPGPEEK (SEQ ID NO: 1) , wherein the isolated epitope or epitope segment consists of:(i) KVNPQGPGPEEK (SEQ ID NO: 1);(ii) a fragment of KVNPQGPGPEEK (SEQ ID NO: 1) consisting of VNPQGPGPEEK (SEQ ID NO: 2), VNPQGPGPEE (SEQ ID NO: 3), NPQGPGPEE (SEQ ID NO: 4), KVNPQGPGPE (SEQ ID NO: 5) or KVNPQGPGP (SEQ ID NO: 6); position 1, wherein V (val) is substituted with any other amino acid,', 'position 2, wherein N (asn) is substituted with any other amino acid,', 'position 3, wherein P (pro) is substituted with any other amino acid,', 'position 4, wherein Q (gln) is substituted with any one of Y (tyr), A (ala), E (glu), V (val), M (met), F (phe), L (leu), I (ile), T (thr), or R (arg), position 5, wherein G (gly) is substituted with A (ala), S (ser), T (thr), H (his), W (trp), Y (tyr), F (phe), or M (met),', 'position 8, wherein P (pro) is substituted with any other amino acid,', 'position 10, wherein E (glu) is substituted with Q (gln), D (asp), F (phe), H (his) or M (met),, '(iii) a variant of SEQ ID NO: 3 with a substitution at any one or more of position 1, wherein N (asn) is substituted with H (his),', 'position 2, wherein P (pro) is substituted with any other amino acid,', 'position 3, wherein Q (gln) is substituted with any one of N (asn), M (met), T (thr), S (ser), or R (arg),', 'position 5, wherein P (pro) is substituted with A (ala),', 'position 7, wherein P (pro) is substituted with any one of A (ala), D (asp), C (cys), E (glu), Z (glx), G (gly), H (his), K (lys), M (met), F (phe), P (pro), S (ser), T (thr), W (trp), or Y (tyr),', 'position 9, wherein E (glu) is substituted with any other amino acid; or, '(iv) a variant of SEQ ID NO: 4 with a substitution at any one or more of position 1, wherein K ...

CHIMERIC ANTIGEN RECEPTORS, COMPOSITIONS, AND METHODS

This disclosure describes chimeric antigen receptors for expression in a Natural Killer (NK) cell, pharmaceutical compositions that include NK cells (and/or iPSCs) modified to express a chimeric antigen receptor, and methods involving such chimeric antigen receptors. Generally, the chimeric antigen receptor includes an ectodomain that includes an antigen recognition region, a transmembrane domain linked to the ectodomain, and an endodomain linked to the transmembrane domain. The endodomain can include a signaling peptide that activates an NK cell. 1. A chimeric antigen receptor comprising:an ectodomain comprising an antigen recognition region;a transmembrane domain linked to the ectodomain; andan endodomain linked to the transmembrane domain, the endodomain comprising a signaling peptide that activates an NK cell.2. The chimeric antigen receptor of wherein the antigen recognition domain specifically binds an antigen associated with a disease.3. The chimeric antigen receptor of wherein the antigen recognition domain specifically binds a tumor antigen.4. The chimeric antigen receptor of wherein the ectodomain further comprises a signal peptide or leader sequence.5. The chimeric antigen receptor of wherein the ectodomain further comprises a spacer.6. The chimeric antigen receptor of wherein the endodomain comprises a signaling domain of and NK cell membrane-bound signaling adaptor protein.7. The chimeric antigen receptor of wherein the NK cell membrane-bound signaling adaptor protein comprises at least a portion of 2B4 (CD244) claim 6 , CD137 (41BB) claim 6 , IL21 claim 6 , DAP10 claim 6 , DAP12 claim 6 , or CD3ζ.8. The chimeric antigen receptor of wherein the transmembrane domain comprises a transmembrane region of a natural cytotoxicity receptor expressed in NK cells.9. The chimeric antigen receptor of wherein the natural cytotoxicity receptor expressed in NK cells comprises at least a portion of CD16 claim 8 , NKp44 claim 8 , NKp46 claim 8 , NKG2D claim 8 , NKp30 ...

PEPTIDES BINDING TO BFL-1

This disclosure features stapled peptide inhibitors (e.g., cysteine-reactive stapled peptides) of the anti-apoptotic protein, BFL-1, and methods of using same in the treatment of BFL-1 expressing cancers. 1. A polypeptide that binds to Bfl-1 , the polypeptide comprising an amino acid sequence set forth in SEQ ID NOs.: 22-36 , , or SEQ ID NOs.: 41-119.3. The compound of claim 2 , wherein Ris selected from the group consisting of: 3S-1-pyrrolidine-3-carboxylic acid terminating in acrylamide; D-homoproline terminating in acrylamide; L-homoproline terminating in acrylamide; isonipecotic acid terminating in acrylamide; D-nipecotic acid terminating in acrylamide; L-nipecotic acid terminating in acrylamide; D-proline terminating in acrylamide; L-proline terminating in acrylamide; trans-4-dimethylaminocrotonic acid terminating in acrylamide; and acrylic acid.4. The compound of claim 2 , wherein Ris a Calkylene.5. The compound of claim 2 , wherein the compound binds to BFL-1 claim 2 , preferably wherein the compound covalently binds to BFL-1.7. The internally cross-linked peptide of claim 6 , wherein Ris a Calkylene.8. The internally cross-linked peptide of claim 6 , wherein the compound binds to BFL-1.9. A method for treating a patient suffering from a cancer that exhibits expression of BFL-1 claim 1 , the method comprising administering a therapeutically effective amount of the compound of to the patient.10. The method of claim 9 , wherein the cancer is a melanoma or other solid tumor.11. The method of claim 9 , wherein the cancer is a leukemia or lymphoma.12. A method for treating a patient suffering from a cancer that exhibits expression of BFL-1 claim 6 , the method comprising administering a therapeutically effective amount of the internally cross-linked peptide of to the patient.13. A method for treating a patient suffering from a cancer that exhibits dependency on BFL-1 claim 1 , the method comprising administering a therapeutically effective amount of the compound ...

Novel generation of antigen-specific tcrs

The present invention contemplates methods for the generation of human antigen-specific T lymphocytes. The methods employ MHC class-II targeting signals fused to an antigen or fragment thereof to obtain MHC class presentation of RNA coded proteins. Accordingly, the present invention concerns expression vectors comprising MHC class-II targeting signal and at least one antigen or fragment thereof and its use for the in vitro generation of antigen-specific T lymphocytes. T cell clones and T cell receptors (TCRs) specific for tumor antigens or viral antigens are also described.

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST VARIOUS TUMORS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of eliciting an immune response in a patient who has cancer , comprising administering to said patient a population of activated T cells that selectively recognize cells that aberrantly express a peptide consisting of the amino acid sequence selected from the group consisting of SEQ ID NO: 1 , from SEQ ID NO: 3 to SEQ ID NO: 10 , SEQ ID NO: 12 , SEQ ID NO: 13 , from SEQ ID NO: 15 to SEQ ID NO: 23 , from SEQ ID NO: 26 to SEQ ID NO: 42 , from SEQ ID NO: 44 to SEQ ID NO: 83 , from SEQ ID NO: 85 to SEQ ID NO: 116 , from SEQ ID NO: 118 to SEQ ID NO: 156 , from SEQ ID NO: 158 to SEQ ID NO: 232 , from SEQ ID NO: 234 to SEQ ID NO: 242 , SEQ ID NO: 244 , from SEQ ID NO: 247 to SEQ ID NO: 252 , from SEQ ID NO: 254 to SEQ ID NO: 263 , and from SEQ ID NO: 265 to SEQ ID NO: 288;wherein said cancer is selected from the group consisting of hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, non-small cell lung cancer (NSCLC), pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), chronic lymphocytic leukemia (CLL), Merkel cell carcinoma (MCC), small cell lung cancer (SCLC), Non-Hodgkin ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST ESOPHAGEAL CANCER AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of eliciting an immune response in a patient who has cancer , comprising administering to said patient a population of activated T cells that selectively recognize cells , which present a peptide consisting of the amino acid sequence of SEQ ID NO: 67 ,wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC molecule on the surface of the antigen presenting cell, for a period of time sufficient to activate said T cell, andwherein said cancer is selected from the group consisting of esophageal cancer, lung cancer, urinary bladder cancer, ovarian cancer, melanoma, uterine cancer, hepatocellular cancer, renal cell cancer, brain cancer, colorectal cancer, breast cancer, gastric cancer, pancreatic cancer, gallbladder cancer, bile duct cancer, prostate cancer, and leukemia.2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.5. The method of claim 1 , wherein the activated T cells are expanded in vitro.6. The ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST ESOPHAGEAL CANCER AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of eliciting an immune response in a patient who has cancer , comprising administering to said patient a population of activated T cells that selectively recognize cells which present a peptide consisting of the amino acid sequence of SEQ ID NO: 32 ,wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC molecule on the surface of the antigen presenting cell, andwherein said cancer is selected from the group consisting of esophageal cancer, lung cancer, urinary bladder cancer, ovarian cancer, melanoma, uterine cancer, hepatocellular cancer, renal cell cancer, brain cancer, colorectal cancer, breast cancer, gastric cancer, pancreatic cancer, gallbladder cancer, bile duct cancer, prostate cancer, and leukemia.2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.5. The method of claim 1 , wherein the activated T cells are expanded in vitro.6. The method of claim 1 , wherein the MHC molecule is an MHC class I ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST LUNG CANCER, INCLUDING NSCLC, SCLC AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of eliciting an immune response in a patient who has lung cancer , comprising administering to the patient a population of activated T cells that selectively recognize cells that present a peptide consisting of the amino acid sequence of SEIEQEIGSL (SEQ ID NO: 478).2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.5. The method of claim 1 , wherein the activated T cells are expanded in vitro.6. The method of claim 1 , wherein the population of activated T cells are administered in the form of a composition.7. The method of claim 6 , wherein the composition further comprises an adjuvant.8. The method of claim 7 , wherein the adjuvant is selected from anti-CD40 antibody claim 7 , imiquimod claim 7 , resiquimod claim 7 , GM-CSF claim 7 , cyclophosphamide claim 7 , sunitinib claim 7 , bevacizumab claim 7 , interferon-alpha claim 7 , interferon-beta claim 7 , CpG oligonucleotides and derivatives claim 7 , poly-(I:C) and derivatives claim 7 , RNA claim 7 , sildenafil claim 7 , particulate formulations with poly(lactide ...

CELL FOR USE IN IMMUNOTHERAPY WHICH CONTAINS MODIFIED NUCLEIC ACID CONSTRUCT ENCODING WILMS TUMOR GENE PRODUCT OR FRAGMENT THEREOF, METHOD FOR PRODUCING SAID CELL, AND SAID NUCLEIC ACID CONSTRUCT

A cell of the present invention contains a nucleic acid construct encoding a WT1 gene product or a fragment of the WT1 gene product. The nucleic acid construct contains (i) a region encoding a desired fragment of the WT1 gene product and (ii) only AUG as a functional start codon. The present invention can provide a cell into which the nucleic acid construct is introduced so that an expression level of a WT1 gene product or a fragment of the WT1 gene product is remarkably enhanced. 1. A cell for immunotherapy , comprising:a nucleic acid construct encoding a Wilms tumor gene product or a fragment of the Wilms tumor gene product,the nucleic acid construct including (i) a region encoding a fragment of the Wilms tumor gene product, the fragment being indicated by positions 194 to 493 of SEQ ID NO: 1 or by positions corresponding to the positions 194 to 493 of a sequence corresponding to SEQ ID NO: 1 and (ii) only one AUG as a functional start codon, connected to a 5′ terminal side of the region via 3m (m is 0 or a positive integer) bases intervening between the 5′ terminal side of the region and the AUG as the functional start codon.2. The cell as set forth in claim 1 , wherein:as the region encoding the fragment of the Wilms tumor gene product, the nucleic acid construct includes a region encoding a fragment of the Wilms tumor gene product, the fragment being indicated by positions 69 to 517 of SEQ ID NO: 1 or by positions corresponding to the positions 69 to 517 of a sequence corresponding to SEQ ID NO: 1; andthe nucleic acid construct is such that all of CUG at positions 191 to 193 are deleted or C of CUG at positions 191 to 193 is substituted with A in the sequence indicated by SEQ ID NO: 2.3. The cell as set forth in claim 1 , wherein a production amount of proteins directly translated from the nucleic acid construct is 25 times or more as large as that of proteins directly translated from RNA including a coding region indicated by positions 191 to 1741 of SEQ ID NO ...

Method for Identifying and Treating Cancer

A new system for identification and treatment against cancer, specifically the mutation or deletion of an antioncogene. An ideal candidate is a patient with family history for hereditary mutations in a known antioncogene. The first method of this system identifies the mutation of a patient's at-risk antioncogene by causing a natural fluorescence only when the specific at-risk antioncogene has mutated or deleted. The second method of this system utilizes a virus to attack and dissolve cancer cells with special markers to avoid the damage to normal cells, thereby achieving the purpose of treating cancer.

Consensus Prostate Antigens, Nucleic Acid Molecule Encoding The Same And Vaccine And Uses Comprising The Same

Provided herein are consensus amino acid sequences of prostate antigens that are capable of breaking tolerance in a targeted species, including PSA, PSMA, STEAP and PSCA antigens. Also provided are nucleic acid sequences that encode one or more consensus amino acid sequences of prostate antigens PSA, PSMA, STEAP and PSCA, as well as genetic constructs/vectors and vaccines expressing the sequences. Also provided herein are methods for generating an autoimmune response against prostate cancer cells by administering one or more of the vaccines, proteins, and/or nucleic acid sequences that are provided.

ALBUMIN-PROAEROLYSIN PRODRUGS

The present invention relates to the field of cancer. More specifically, the present invention provides compositions and methods for treating cancer using albumin-proaerolysin prodrugs. Accordingly, in one aspect, the present invention provides prodrug compositions. In certain embodiments, a prodrug composition comprises a prostate-specific antigen (PSA)-activated pro-aerolysin (PA), wherein a PSA cleavable linker replaces the native furin cleavage site within PA; and human serum albumin (HSA) or a fragment thereof fused to the N-terminus of the PSA-activated PA. 1. A prodrug composition comprising:a. a prostate-specific antigen (PSA)-activated pro-aerolysin (PA), wherein a PSA cleavable linker replaces the native furin cleavage site within PA; andb. human serum albumin (HSA) or a fragment thereof fused to the N-terminus of the PSA-activated PA.2. The composition of claim 1 , wherein the PSA cleavable linker comprises SEQ ID NO:5.3. The composition of claim 1 , wherein the PSA cleavable linker replaces the amino acids at position 427-432 of SEQ ID NO:2.4. The composition of claim 1 , wherein the HSA or fragment thereof comprises the C-terminal end of HSA.5. The composition of claim 1 , wherein the HSA or fragment thereof comprises SEQ ID NO:27.6. The composition of claim 1 , wherein the HSA or fragment thereof is fused to the N-terminus of the PSA-activated PA with at least one PSA-cleavable linker sequence.7. The composition of claim 6 , wherein the at least one PSA-cleavable linker sequence comprises SEQ ID NO:5.8. The composition of claim 6 , wherein the HSA or fragment thereof is fused to the N-terminus of the PSA-activated PA with four identical PSA-cleavable linker sequences claim 6 , wherein the linker sequence comprises SEQ ID NO:5.9. A recombinant protein comprises SEQ ID NO:48.10. The protein of claim 9 , wherein the protein further comprises a polyhistidine tag.11. The protein of claim 10 , wherein the polyhistidine tag comprises six histidines at the C- ...

Id4 protein restores wild type p53 activity

A compound and method for treating cancer, in particular prostate cancer. Id4 reverts mutant p53 activity to its wild type physiological status and activity. Id4 or its peptidemimatics are used to revert mutant p53 to wild type p53, restoring its tumor suppressor activity.

METHOD AND COMPOSITIONS FOR ENHANCING IMMUNOTHERAPEUTIC TREATMENT OF A CANCER

Provided are methods and compositions for enhancing treatment of a cancer by administering a therapeutic agent for the treatment of a cancer together with a second agent that elevates the level of protein p53. The second agent generates in the tumor a population of dendritic cells expressing at least one of Batf3, IRF5, CD103, and XCR1. The second therapeutic agent can also suppress an autoimmune response to non-cancerous tissue in the patient if generated by an immunotherapeutic agent. The method can further comprise administering a PTEN phosphatase inhibitor. 1. A method for enhancing a therapeutic treatment of a cancer , said method comprising the steps of:(a) administering to a patient in need thereof a therapeutic dose of a first therapeutic agent for the treatment of a cancer in said patient; and(b) administering to the patient a therapeutic dose of a second therapeutic agent that elevates the level of protein p53 in said patient.2. The method of claim 1 , wherein the first therapeutic agent is an immunotherapeutic agent or a cytotoxic agent.3. The method of claim 1 , wherein the second therapeutic agent generates in a tumor a population of dendritic cells expressing at least one of Batf3 claim 1 , IRF5 claim 1 , CD103 claim 1 , and XCR1.4. The method of claim 2 , wherein the second therapeutic agent suppresses an autoimmune response to non-cancerous tissue in the patient generated by the immunotherapeutic agent.5. The method of claim 2 , wherein the first therapeutic agent is an immunotherapeutic agent and the second therapeutic agent enhances the immunotherapeutic response directed against a tumor in the patient.6. The method of claim 1 , further comprising administering to the patient a therapeutic dose of a PTEN phosphatase inhibitor.7. The method of claim 1 , wherein the second therapeutic agent is a Mouse Double Minute 2 (MDM2) (E3 ubiquitin-protein ligase) MDM2-related protein homolog inhibitor.8. The method of claim 7 , wherein the MDM2-related protein ...

NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS OF THE BLOOD, SUCH AS ACUTE MYELOID LEUKEMIA (AML)

The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to several novel peptide sequences and their variants derived from HLA class I and HLA class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

STABILIZED ALPHA HELICAL PEPTIDES AND USES THEREOF

Novel polypeptides and methods of making and using the same are described herein. The polypeptides include cross-linking (“hydrocarbon stapling”) moieties to provide a tether between two amino acid moieties, which constrains the secondary structure of the polypeptide. The polypeptides described herein can be used to treat diseases characterized by excessive or inadequate cellular death. 137-. (canceled)39. The α-helix containing polypeptide of claim 38 , wherein —(CH)(CH)— is Calkyl or Calkyl.40. The α-helix containing polypeptide of claim 38 , wherein —(CH)(CH)— is Calkenyl or Calkenyl.41. The α-helix containing polypeptide of claim 38 , wherein Rand Rare independently H or Calkyl.42. The α-helix containing polypeptide of claim 38 , wherein the polypeptide comprises a BH3 domain.43. The α-helix containing polypeptide of claim 38 , wherein x is 3 or 6 claim 38 , and z is 1.44. The α-helix containing polypeptide of claim 38 , wherein each y is independently an integer between 1 and 15.45. The α-helix containing polypeptide of claim 38 , wherein Rand Rare independently C-Calkyl.46. The α-helix containing polypeptide of claim 45 , wherein at least one of Rand Ris methyl.47. The α-helix containing polypeptide of claim 38 , wherein x is 3 or 6 claim 38 , and Rand Rare methyl.48. The α-helix containing polypeptide of claim 38 , wherein the polypeptide comprises an amino acid sequence which is at least about 60% identical to the amino acid sequence of SEQ ID NO:1 claim 38 , or an amino acid sequence which is at least about 80% identical to the amino acid sequence of SEQ ID NO:2.49. The α-helix containing polypeptide of claim 48 , wherein at least one of Rand Ris Calkyl.50. The α-helix containing polypeptide of claim 38 , further comprising a fluorescent moiety claim 38 , a radioisotope claim 38 , an affinity label claim 38 , a targeting moiety or a biotin moiety.51. The α-helix containing polypeptide of claim 38 , wherein the polypeptide is selected from the group ...

KIDNEY-SPECIFIC TUMOR VACCINE DIRECTED AGAINST KIDNEY TUMOR ANTIGEN G-250

This invention provides an anti-cancer immunogenic agent(s) (e.g. vaccines) that elicit an immune response specifically directed against renal cell cancers expressing a G250 antigenic marker. Preferred immunogenic agents comprise a chimeric molecule comprising a kidney cancer specific antigen (G250) attached to a granulocyte-macrophage colony stimulating factor (GM-CSF). The agents are useful in a wide variety of treatment modalities including, but not limited to protein vaccination, DNA vaccination, and adoptive immunotherapy. 117-. (canceled)18. A nucleic acid encoding a fusion protein comprising a G250 kidney cancer specific antigen attached to a granulocyte macrophage colony stimulating factor (GM-CSF).19. The nucleic acid of claim 18 , wherein said nucleic acid is a deoxyribonucleic acid (DNA).20. The nucleic acid of claim 18 , wherein the G250 antigen is a human G250 antigen and the GM-CSF is a human GM-CSF.21. The nucleic acid of claim 20 , wherein the G250 antigen and the GM-CSF are joined by a peptide linker ranging in length from 2 to about 20 amino acids.22. The nucleic acid of claim 21 , wherein said peptide linker is -Arg-Arg-.23. The nucleic acid of claim 22 , wherein said nucleic acid encodes the polypeptide of SEQ ID NO: 1.24. The nucleic acid of claim 22 , wherein said nucleic acid comprises the nucleic acid of SEQ ID NO: 2.25. The nucleic acid of claim 20 , wherein said nucleic acid is present in an expression cassette.26. The nucleic acid of claim 20 , wherein said nucleic acid is present in a vector.27. (canceled)28. A host cell transfected with a nucleic acid comprising the nucleic acid of .29. The host cell of claim 28 , wherein said host cell is a eukaryotic cell.30. (canceled)31. A method of producing an anti-tumor vaccine claim 18 , said method comprising: culturing a cell transfected with a nucleic acid comprising the nucleic acid of under conditions where said nucleic expresses a G250-GM-CSF fusion protein; and recovering said fusion ...

IMMUNOGENIC POTE PEPTIDES AND METHODS OF USE

POTE has recently been identified as a tumor antigen expressed in a variety of human cancers, including colon, ovarian, breast, prostate, lung and pancreatic cancer. Described herein are immunogenic POTE polypeptides, including modified POTE polypeptides, that bind MHC class I molecules. The immunogenic POTE polypeptides are capable of inducing an immune response against POTE-expressing tumor cells. Thus, provided herein is a method of eliciting an immune response in a subject, such as a subject having a type of cancer that expresses POTE. 1. An isolated nucleic acid molecule encoding an immunogenic polypeptide , wherein the polypeptide comprises no more than 10 consecutive amino acids of the amino acid sequence of human POTE set forth as:{'sub': 1', '2', '3', '4', '5', '6', '7', '8', '9', '10', '11, 'MVAEVCSMPTASTVKKPFDLRSKMGKWCHHRFPCCRGSGKSNMGTSG DHDDSFMKMLRSKMGKCCRHCFPCCRGSGTSNVGTSGDHENSFMKML RSKMGKWCCHCFPCCRGSGKSNVGAWGDYDHSAFMEPRYHIRREDLD KLHRAAWWGKVPRKDLIVMLRDTDMNKRDKEKRTALHLASANGNSE VVQLLLDRRCQLNVLDNKKRTALIKAIQCQEDECVLMLLEHGADRNIPD EYGNTALHYAIYNEDXLXAKAXLXYGADIESKNKCGLTPLLLGVHE QKQQVVKFLIKKKANLNVLDRYGRTALILAVCCGSASIVNXLXEQNXDVSSQDLSGQTAREYAVSSHHHVICELLSDYKEKQMLKISSENSNPEQD LKLTSEEESQRLKVSENSQPEKMSQEPEINKDCDREVEEEIKKHGSNPVG LPENLTNGASAGNGDDGLIPQRRSRKPENQQFPDTENEEYHSDEQNDTR KQLSEEQNTGISQDEILTNKQKQIEVAEQKMNSELSLSHKKEEDLLRENS VLQEEIAMLRLELDETKHQNQLRENXXXEEIXSVKEKTDKLLRAM QLNEEALTKTNI (SEQ ID NO: 20),'}{'sub': 1', '2', '3', '4', '5, 'wherein Xis K or Y; Xis M, A or F; Xis L or A; Xis L or V; Xis L or Y;'}{'sub': 6', '7', '8', '9', '10', '11, 'Xis L, A or F; Xis V, or A; Xis K or Y; Xis I or L; Xis L or F; and Xis E or A; and'}wherein the polypeptide comprises one of (a) amino acids 323-331; (b) amino acids 222-230; (c) amino acids 252-260; (d) amino acids 272-280; or (e) amino acids 553-561 of SEQ ID NO: 20, wherein the polypeptide does not comprise the amino acid sequence KLMAKALLL (SEQ ID NO: 3).2. The isolated nucleic acid molecule of claim 1 , wherein the ...

Vectors and methods for the efficient generation of integration/transgene-free induced pluripotent stem cells from peripheral blood cells

A vector for generating induced pluripotent stem cells from human target cells comprising a) a vector backbone, b) exactly two, three or four transcription and reprogramming factor genes, each gene separated by a 2a self-cleavage peptide sequence, c) a spleen focus-forming virus promoter, and d) a post-transcriptional regulatory element Wpre, with or without an anti-apoptotic factor gene. A method for generating integration-free induced pluripotent stem cells, the method comprising: a) providing target cells, b) providing one or more than one vector according to the present invention, c) transducing or transfecting the target cells with the one or more than one vector, and d) culturing the transduced or transfected cells in a cell culture, thereby generating integration-free induced pluripotent stem cells.

Peptides and combination of peptides for use in immunotherapy against cancers

The present description relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present description relates to the immunotherapy of cancer. The present description further relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T-cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

H3.3 CTL Peptides and Uses Thereof

Peptides that generate an immune response to glioma-related H3.3 proteins and methods of their use are provided. 1. A modified T-cell comprising a heterologous T-cell receptor (TCR) or fragment thereof which binds a histone H3 variant H3.3 peptide , wherein the TCR or fragment thereof comprises:a TCR alpha chain or fragment thereof comprising complementarity determining regions (CDRs) 1, 2, and 3 comprising SEQ ID NOs: 12, 13, and 14, respectively; anda TCR beta chain or fragment thereof comprising CDRs 1, 2, and 3 comprising SEQ ID NOs: 15, 16, and 17, respectively.2. The T-cell of claim 1 , wherein the TCR alpha chain or fragment thereof is a TCR alpha chain and the TCR beta chain or fragment thereof is a TCR beta chain.3. The T-cell of claim 2 , wherein the TCR alpha chain comprises the amino acid sequence set forth in SEQ ID NO: 8 claim 2 , and the TCR beta chain comprises the amino acid sequence set forth in SEQ ID NO: 10.4. The T-cell of claim 3 , wherein the heterologous TCR is expressed from a nucleic acid comprising a polynucleotide sequence encoding a self-cleaving peptide that links polynucleotide sequences encoding the TCR alpha and beta chains.5. The T-cell of claim 4 , wherein the self-cleaving peptide is a porcine teschovirus-1 2A (P2A) peptide.6. The T-cell of claim 1 , wherein the heterologous TCR is expressed from a retroviral vector.7. The T-cell of claim 6 , wherein the retroviral vector is a lentiviral vector.8. The T-cell of claim 7 , wherein the T-cell exhibits downregulated expression of an endogenous T-cell receptor comprising an endogenous TCR alpha chain and an endogenous TCR beta chain.9. The T-cell of claim 8 , whereini) the T-cell exhibits downregulated expression of an endogenous TCR alpha chain;ii) the T-cell exhibits downregulated expression of an endogenous TCR beta chain; oriii) the T-cell exhibits downregulated expression of an endogenous TCR alpha chain and downregulated expression of an endogenous TCR beta chain.10. The T-cell ...

Novel peptides and combination of peptides for use in immunotherapy against breast cancer and other cancers

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

FUSION POLYNUCLEOTIDES AND FUSION POLYPEPTIDES ASSOCIATED WITH CANCER AND PARTICULARLY MELANOMA AND THEIR USES AS THERAPEUTIC AND DIAGNOSTIC TARGETS

Novel fusion molecules and uses are disclosed. 1. An isolated or purified nucleic acid molecule that encodes a fusion , or a breakpoint comprising fragment thereof , chosen from CLIP1-ROS1; PPFIBP1-ROS1; TPM3-ROS1; ZCCHC8-ROS1; MYO5A-ROS1; PWWP2A-ROS1; HLA-A-ROS1; ERC1-ROS1; TPM3-ALK; GOLGA5-RET; CEP89-BRAF; KIF5B-RET; or TP53-NTRK1 , summarized in , or a sequence at least 85% identical thereto.2. A nucleic acid molecule that is capable of hybridizing to a fusion comprising the nucleotide sequence of CLIP1-ROS1; PPFIBP1-ROS1; TPM3-ROS1; ZCCHC8-ROS1; MYO5A-ROS1; PWWP2A-ROS1; HLA-A-ROS1; ERC1-ROS1; TPM3-ALK; GOLGA5-RET; CEP89-BRAF; KIF5B-RET; or TP53-NTRK1 , summarized in , or a fragment thereof comprising a breakpoint.32. A fragment of the nucleic acid molecule of either of - claims 1 , wherein said fragment comprises oligonucleotides between 10 and 25 nucleotides in length claims 1 , or between 100 to 300 nucleotides in length.4. The fragment of claim 3 , which is a probe or primer that includes an oligonucleotide between about 5 and 25 nucleotides in length.5. The fragment of claim 3 , which is a bait that comprises an oligonucleotide between about 100 to 300 nucleotides claim 3 , 130 and 230 nucleotides claim 3 , or 150 and 200 nucleotides claim 3 , in length.65. A nucleic acid molecule of any of - suitable as probe claims 1 , primer claims 1 , bait or library member that specifically binds to the fusion.75. The isolated or purified nucleic acid molecule of any of - claims 1 , which is operatively linked to a native or a heterologous regulatory sequence.85. An isolated or purified vector comprising a nucleic acid molecule of any of -.9. A host cell comprising a vector of .102. A nucleic acid molecule that specifically reduces or inhibits the expression of the nucleic acid molecule of any of -.11. The nucleic acid molecule of claim 10 , which is chosen from an antisense molecule claim 10 , ribozyme claim 10 , siRNA claim 10 , or triple helix molecule.12. An ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST PROSTATE CANCER AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A peptide comprising an amino acid sequence selected from the group consisting of SEQ ID No. 1 to SEQ ID No. 48 , and variant sequences thereof which are at least 88% homologous to SEQ ID No. 1 to SEQ ID No. 48 , wherein said variant binds to molecule(s) of the major histocompatibility complex (MHC) and/or induces T cells cross-reacting with said variant peptide; and a pharmaceutical acceptable salt thereof , wherein said peptide is not a full-length polypeptide.2. The peptide or variant according to claim 1 , wherein said peptide has the ability to bind to a MHC class-I or -II molecule claim 1 , and wherein said peptide claim 1 , when bound to said MHC claim 1 , is capable of being recognized by CD4 and/or CD8 T cells.3. The peptide or variant thereof according to claim 1 , wherein the amino acid sequence thereof comprises a continuous stretch of amino acids according to the group of SEQ ID No. 1 to SEQ ID No. 48.4. The peptide or variant thereof according to claim 1 , wherein said peptide or variant thereof has an overall length of from 8 to 100 claim 1 , optionally from 8 to 30 claim 1 , and optionally from 8 to 16 amino acids claim 1 , and optionally wherein the peptide consists or consists essentially of an amino acid sequence according to the group of ...

Synthetic promoters for high throughput screening and gene modulation

The present invention provides nucleic acid constructs, expression vectors, transgenic cell and methods of making and using the same, wherein the nucleic acid construct includes a synthetic promoter designed from the endogenous promoter of BIRC5 and LAMC2. In illustrative working embodiments of the invention, an exogenous nucleic acid fragment encoding thymidine kinase is operably linked to the synthetic promoter which is then shown to regulate the expression of this polypeptide.

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST OVARIAN CANCER AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method for killing target cells in a patient who has cancer , comprising administering to the patient an effective number of activated T cells that selectively recognize a cancer cell , which presents a peptide consisting of the amino acid sequence of SEQ ID NO: 196 , 2-7 , 9-52 , 54-195 , or 197-772 ,wherein said cancer is selected from the group consisting of ovarian cancer, breast cancer, cholangiocellular carcinoma, colorectal cancer, gastric cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, melanoma, non-Hodgkin lymphoma, non-small cell lung cancer, esophageal cancer, pancreatic cancer, small cell lung cancer, urinary bladder carcinoma, and uterine and endometrial cancer.2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.5. The method of claim 1 , further comprising administering to the patient an adjuvant selected from anti-CD40 antibody claim 1 , imiquimod claim 1 , resiquimod claim 1 , GM-CSF claim 1 , cyclophosphamide claim 1 , sunitinib claim 1 , bevacizumab claim 1 , interferon-alpha ...

Novel peptides and combination of peptides for use in immunotherapy against lung cancer, including NSCLC, SCLC and other cancers

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A peptide comprising an amino acid sequence selected from the group consisting of (i) SEQ ID No. 1 to SEQ ID No. 489 , and/or a variant sequence thereof which is at least 88% homologous to SEQ ID No. 1 to SEQ ID No. 489 , and wherein said variant binds to molecule(s) of the major histocompatibility complex (MEW) and/or induces T cells cross-reacting with said variant peptide , and/or (ii) a pharmaceutical acceptable salt thereof , wherein said peptide is not a full-length polypeptide.2. The peptide according to claim 1 , wherein said peptide has the ability to bind to an MEW class-I or -II molecule claim 1 , and wherein said peptide claim 1 , when bound to said MEW claim 1 , is capable of being recognized by CD4 and/or COB T cells.3. The peptide according to claim 1 , wherein the amino acid sequence thereof comprises a continuous stretch of amino acids according to any one of SEQ ID No. 1 to SEQ ID No. 489.4. The peptide according to claim 1 , wherein said peptide has an overall length of from 8 to 100 claim 1 , optionally from 8 to 30 claim 1 , and optionally from 0.8 to 16 amino acids claim 1 , and optionally wherein the peptide consists or consists essentially of an amino acid sequence according to any of SEQ ID No. 1 to SEQ ID No. 489.5. The peptide ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST ESOPHAGEAL CANCER AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of eliciting an immune response in a patient who has cancer , comprising administering to said patient a population of activated T cells that selectively recognize cells , which present a peptide consisting of the amino acid sequence of SEQ ID NO: 11 ,wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC molecule on the surface of the antigen presenting cell,wherein said cancer is selected from the group consisting of esophageal cancer, lung cancer, urinary bladder cancer, ovarian cancer, melanoma, uterine cancer, hepatocellular cancer, renal cell cancer, brain cancer, colorectal cancer, breast cancer, gastric cancer, pancreatic cancer, gallbladder cancer, bile duct cancer, prostate cancer, and leukemia.2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.5. The method of claim 1 , wherein the activated T cells are expanded in vitro.6. The method of claim 1 , wherein the MHC molecule is an MHC class I ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST ESOPHAGEAL CANCER AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of eliciting an immune response in a patient who has cancer , comprising administering to said patient a population of activated T cells that selectively recognize cells , which present a peptide consisting of the amino acid sequence of SEQ ID NO: 12 ,wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC molecule on the surface of the antigen presenting cell, andwherein said cancer is selected from the group consisting of esophageal cancer, lung cancer, urinary bladder cancer, ovarian cancer, melanoma, uterine cancer, hepatocellular cancer, renal cell cancer, brain cancer, colorectal cancer, breast cancer, gastric cancer, pancreatic cancer, gallbladder cancer, bile duct cancer, prostate cancer, and leukemia.2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.5. The method of claim 1 , wherein the activated T cells are expanded in vitro.6. The method of claim 1 , wherein the MHC molecule is an MHC class I ...

NOVEL PEPTIDES, COMBINATION OF PEPTIDES AS TARGETS AND FOR USE IN IMMUNOTHERAPY AGAINST GALLBLADDER CANCER AND CHOLANGIOCARCINOMA AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method for killing target cells in a patient , comprising administering to the patient a population of activated T cells that kill a target cell that presents a peptide consisting of the amino acid sequence of SEQ ID NO: 2 , 8 , 3 , 13 , 1 , 4 , 7 , 9-12 , 15-17 , or 19-38 on the cell surface.2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the activated T cells are produced by contacting T cells with the peptide loaded human class I or II MHC molecules expressed on the surface of an antigen-presenting cell for a period of time sufficient to activate the T cells.5. The method of claim 1 , wherein the activated T cells are expanded in vitro.6. The method of claim 1 , wherein the peptide is in a complex with an MHC class I molecule.7. The method of claim 4 , wherein the antigen presenting cell is infected with a recombinant virus expressing the peptide.8. The method of claim 7 , wherein the antigen presenting cell is a dendritic cell or a macrophage.9. The method of claim 5 , wherein the expansion is in the presence of an anti-CD28 antibody and IL-12.10. The method of claim 1 , wherein the population of activated T ...

NOVEL PEPTIDES AND COMBINATION OF PEPTIDES FOR USE IN IMMUNOTHERAPY AGAINST ESOPHAGEAL CANCER AND OTHER CANCERS

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules. 1. A method of treating a patient who has a cancer overexpressing PRDM15 polypeptide comprising the amino acid sequence of SEQ ID NO: 82 , comprising administering to said patient a composition comprising a population of activated T cells that kill cancer cells ,wherein the activated T cells are cytotoxic T cells produced by contacting CD8+ T cells with an antigen presenting cell that presents a peptide consisting of the amino acid sequence of SEQ ID NO: 82 in a complex with an MHC class I molecule on the surface of the antigen presenting cell in vitro, for a period of time sufficient to activate said T cell,wherein said cancer is selected from the group consisting of esophageal cancer, non-small cell lung cancer, liver cancer, leukemia, breast cancer, and kidney cancer.2. The method of claim 1 , wherein the T cells are autologous to the patient.3. The method of claim 1 , wherein the T cells are obtained from a healthy donor.4. The method of claim 1 , wherein the T cells are derived from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.5. The method of claim 1 , further comprising expanding T cells in vitro.6. The method of claim 1 , wherein the composition further comprises an adjuvant.7. The method of claim 6 , wherein the adjuvant is ...

SERINE PROTEASE MOLECULES AND THERAPIES

Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided. 1102.-. (canceled)103. A cell-targeting construct comprising:(a) cytotoxic moiety;(b) an antibody heavy chain constant (Fc) domain; and(c) a cell-targeting hormone domain.104. The cell-targeting construct of claim 103 , wherein the polypeptide comprises from N- to C-terminus (a) the cytotoxic moiety; (b) the Fc domain; and (c) the cell-targeting hormone domain.105. The cell-targeting construct of claim 104 , wherein the cell-targeting hormone domain is human chorionic gonadotropin claim 104 , gonadotropin releasing hormone claim 104 , an androgen claim 104 , an estrogen claim 104 , thyroid-stimulating hormone claim 104 , follicle-stimulating hormone claim 104 , luteinizing hormone claim 104 , prolactin claim 104 , growth hormone claim 104 , adrenocorticotropic hormone claim 104 , antidiuretic hormone claim 104 , oxytocin claim 104 , thyrotropin-releasing hormone claim 104 , growth hormone releasing hormone claim 104 , corticotropin-releasing hormone claim 104 , somatostatin claim 104 , dopamine claim 104 , melatonin claim 104 , thyroxine claim 104 , calcitonin claim 104 , parathyroid hormone claim 104 , glucocorticoids claim 104 , mineralocorticoids claim 104 , adrenaline claim 104 , noradrenaline claim 104 , progesterone claim 104 , insulin claim 104 , glucagon claim 104 , amylin claim 104 , erythropoitin claim 104 , calcitriol claim 104 , calciferol claim 104 , atrial-natriuretic peptide claim 104 , gastrin claim 104 , secretin claim 104 , cholecystokinin claim 104 , neuropeptide Y claim 104 , ghrelin claim 104 , PYY3-36 claim 104 , ...