Chimeric interleukin-6 soluble receptor/ligand proteins

Chimeric proteins constructed from the fusion of the naturally occurring form of the soluble IL-6 receptor and IL-6 which are useful for treatment of cancer and liver disorders, enhancement of bone marrow transplantation, and treatment of other IL-6 related conditions are provided.

Chimeric mammals with human hematopoietic cells

There is disclosed a chimeric mammal having a stable bone marrow graft of human hematopoietic cells capable of differentiating into multiple lineages of human mature cells, wherein at least 30% of the hematopoietic cells in the mammal's bone marrow are of human origin. The inventive method comprises sublethally irradiating an immunodeficient mammal, infusing human hematopoietic cells into the mammal and administering an effective amount of human mast cell growth factor (MGF) and a human granulocyte macrophage colony stimulating factor/interleukin-3 fusion protein (GM-CSF/IL-3 FP) to promote engraftment of human cells within the chimeric mammal's bone marrow.

Chimeric interleukin-6 soluble receptor/ligand protein, analogs thereof and uses thereof

SHORT BETA-DEFENSIN-DERIVED PEPTIDES

The invention is directed to beta-defensin-derived peptides and their use in modulating the activity of hematopoietic cells and other CXCR4-expressing cells. Specifically, the invention provides compositions and methods useful in the treatment of cancer. The invention further provides compositions and methods useful for promoting mobilization and transplantation of hematopoietic stem cells and progenitor cells. 1. A cyclized peptide selected from the group consisting of:(a) 1,10-cyclo[RGRKCCRRKK], (cTL-1, SEQ ID NO: 3), wherein arginine at position 1 is linked through a peptide bond to the lysine at position 10; and(b) a cyclized homolog of SEQ ID NO: 3 having at least 70% sequence homology to SEQ ID NO: 3 and at least 70% identity with regard to the overall positive charge density of SEQ ID NO: 3, wherein the N-terminus and the C-terminus of the peptide are linked through a covalent bond, and wherein the two adjacent cysteines at positions 5 and 6 of SEQ ID NO: 3 are retained.2. The peptide of claim 1 , wherein the homolog has at least 70% of the hydrophilicity/hydrophobicity characteristics of SEQ ID NO: 3.3. A pharmaceutical composition containing an effective amount of the peptide of claim 1 , and one or more pharmaceutically accepted carriers claim 1 , excipients or diluents.4. A pharmaceutical composition containing an effective amount of an isolated peptide having an N-terminus and a C-terminus selected from the group consisting of:(a) RGRKCCRRKK (TL-1, SEQ ID NO: 1);(b) SGRKCCRKKK (AK-1, SEQ ID NO: 2); and(c) a homolog of TL-1, having at least 70% sequence homology to SEQ ID NO: 1, at least 70% identity with regard to the overall positive charge density of SEQ ID NO: 1, wherein the cysteines at positions 5 and 6 of SEQ ID NO: 1 are retained, and wherein said homolog induces or enhances mobilization of hematopoietic progenitor and/or stem cells;and one or more pharmaceutically accepted carriers, excipients or diluents, said composition further comprising at ...

Catecholamine receptor modulation

The invention relates to receptors of catecholamines and their role in stem cell development and function.

Stem cells having increased sensitivity to a chemoattractant and methods of generating and using same

The present invention relates to stem cells which exhibit increased sensitivity to a chemoattractant and, more particularly, to methods of generating and using them such as in clinical applications involving stem cell transplantation.

Catecholamine Receptor Modulation

The invention relates to receptors of catecholamines and their role in stem cell development and function.

Nucleic acids encoding chimeric interleukin-6 soluble receptor/ligand protein, analogs thereof and uses thereof

Chimeric proteins constructed from the fusion of the naturally occurring form of the soluble IL-6 receptor and IL-6 which are useful for treatment of cancer and liver disorders, enhancement of bone marrow transplantation, and treatment of other IL-6 related conditions are provided.

Elastase inhibitor and acute leukemia

The invention relates to the use of an elastase inhibitor in the manufacture of a medicament for the treatment of leukemia, preferably acute leukemia and more preferably for the treatment of AML ...

Stem cells having increased sensitivity to SDF-1 and methods of generating and using same

The present invention relates to stem cells which exhibit increased sensitivity to a chemoattractant and, more particularly, to methods of generating and using them such as in clinical applications involving stem cell transplantation.

MIGRATION OF HEMATOPOIETIC STEM CELLS AND PROGENITOR CELLS TO THE LIVER

The invention relates to transplantation of hematopoietic stem cells (HSC) and/or progenitor cells (HPC) into the liver. More specifically the invention relates to the use of chemokines, preferably SDF-1, for enhancing homing of HSC/HPC to the liver.

Short beta-defensin-derived peptides

The invention is directed to β-defensin-derived peptides and their use in modulating the activity of hematopoietic cells, particularly hematopoietic stem cells and progenitor cells. Specifically, the invention provides compositions and methods useful for promoting mobilization and transplantation of hematopoietic stem cells and progenitor cells. The invention further provides compositions and methods useful in the treatment of cancer.

Stem cells having increased sensitivity to a chemoattractant and methods of generating and using same

The present invention relates to stem cells which exhibit increased sensitivity to a chemoattractant and, more particularly, to methods of generating and using them such as in clinical applications involving stem cell transplantation.

Chimeric Interleukin-6 Soluble Receptor/Ligand Protein, Analogs Thereof and Uses Thereof

Chimeric proteins constructed from the fusion of the naturally occurring form of the soluble IL-6 receptor and IL-6 which are useful for treatment of cancer and liver disorders, enhancement of bone marrow transplantation, and treatment of other IL-6 related conditions are provided.

Stem Cells Suitable for Transplantation, their Preparation and Pharmaceutical Compositions Comprising Them

The present invention relates to stem cells suitable for transplantation and to methods for their preparation.

Stem cells having increased sensitivity to sdf-1 and methods of generating and using same

The present invention relates to stem cells which exhibit increased sensitivity to a chemoattractant and, more particularly, to methods of generating and using them such as in clinical applications involving stem cell transplantation.

Hematopoietic cell composition for use in transplantation

Cell compositions consisting essentially of mammalian hematopoietic CXCR4⁺ stem and progenitor capable to migrate in response to stromal-derived factor 1 (SDF-1) and/or capable to adhere to stromal cells in response to an adhesion-inducing agent, are provided for clinical transplantation. Hematopoietic CXCR4^-/low stem and progenitor cells can be converted into CXCR4⁺ cells by stimulation with a suitable agent. The composition consists preferably of human CD38^-/low CXCR4⁴ cells.

Use of Protease or a Protease Inhibitor for the Manufacture of Medicaments

The invention relates to the use of a cathepsin K inhibitor (CTKI) or CTK, a mutein, isoform, fused protein, functional derivative, active fraction, circularly permutated derivative, a salt or inducer thereof in the manufacture of a medicament for treating a disease in which SDF-1 activity and/or concentration is involved with the development and/or course of the disease.

Stem Cells Suitable for Transplantation, Their Preparation and Pharmaceutical Compositions Comprising Them

The present invention relates to stem cells suitable for transplantation and to methods for their preparation.

Short beta-defensin-derived peptides

The invention is directed to beta-defensin-derived peptides and their use in modulating the activity of hematopoietic cells and other CXCR4-expressing cells. Specifically, the invention provides compositions and methods useful in the treatment of cancer. The invention further provides compositions and methods useful for promoting mobilization and transplantation of hematopoietic stem cells and progenitor cells.

Migration of hematopoietic stem cells and progenitor cells to the liver

The invention relates to transplantation of hematopoietic stem cells (HSC) and/or progenitor cells (HPC) into the liver. More specifically the invention relates to the use of chemokines, preferably SDF-1, for enhancing homing of HSC/HPC to the liver.

Stem cells suitable for transplantation, their preparation and pharmaceutical compositions comprising them

The present invention relates to stem cells suitable for transplantation and to methods for their preparation.

SHORT BETA-DEFENSIN-DERIVED PEPTIDES

The invention is directed to β-defensin-derived peptides and their use in modulating the activity of hematopoietic cells, particularly hematopoietic stem cells and progenitor cells. Specifically, the invention provides compositions and methods useful for promoting mobilization and transplantation of hematopoietic stem cells and progenitor cells. The invention further provides compositions and methods useful in the treatment of cancer. 1. A cyclized peptide selected from the group consisting of:(a) 1,10-cyclo[RGRKCCRRKK], (cTL-1, SEQ ID NO: 3), wherein the arginine at position 1 is linked through a peptide bond to the lysine at position 10; and(b) a cyclized homolog of SEQ ID NO: 3 having at least 70% sequence homology to SEQ ID NO: 3 and at least 70% identity with regard to the overall positive charge density of SEQ ID NO: 3, wherein the N-terminus and the C-terminus of the peptide are linked through a covalent bond, and wherein the two adjacent cysteines at positions 5 and 6 of SEQ ID NO: 3 are retained.2. The peptide of claim 1 , wherein the homolog has at least 70% of the hydrophilicity/hydrophobicity characteristics of SEQ ID NO: 3.3. The peptide of claim 1 , wherein the peptide is cTL-1 (SEQ ID NO: 3).4. A pharmaceutical composition containing an effective amount of the peptide of claim 1 , and one or more pharmaceutically accepted carriers claim 1 , excipients or diluents.5. A method for reducing or inhibiting cancer metastasis in a subject in need thereof claim 1 , comprising administering to the subject an effective amount of a peptide as set forth in .6. The method of claim 5 , wherein the subject is afflicted with a tumor characterized by CXCR5 expression of at least a portion of the tumor cells.7. The method of claim 6 , wherein the tumor is of hematopoietic origin.8. The method of claim 6 , wherein the tumor is leukemia.9. The method of claim 5 , wherein the homolog has at least 70% of the hydrophilicity/hydrophobicity characteristics of SEQ ID NO: 3.10. ...

Short beta-defensin-derived peptides

The invention is directed to β-defensin-derived peptides and their use in modulating the activity of hematopoietic cells, particularly hematopoietic stem cells and progenitor cells. Specifically, the invention provides compositions and methods useful for promoting mobilization and transplantation of hematopoietic stem cells and progenitor cells. The invention further provides compositions and methods useful in the treatment of cancer.

CHIMERIC SOLUBLE INTERLEUKIN-6 RECEPTOR / LIGAND PROTEIN, ANALOG AND USES

Catecholamine receptor modulation

The invention relates to receptors of catecholamines and their role in stem cell development and function.

Stem cells having increased sensitivity to sdf-1 and methods of generating and using same

The present invention relates to stem cells which exhibit increased sensitivity to a chemoattractant and, more particularly, to methods of generating and using them such as in clinical applications involving stem cell transplantation.

Chimeric interleukin-6 soluble receptor/ligand protein, analogs thereof and uses thereof

Chimeric proteins constructed from the fusion of the naturally occurring form of the soluble IL-6 receptor and IL-6 which are useful for treatment of cancer and liver disorders, enhancement of bone marrow transplantation, and treatment of other IL-6 related conditions are provided.

Stem cells having increased sensitivity to SDF-1 and methods of generating and using same

Chimeric mammals with human hematopoietic cells.

The use of a protease or a protease inhibitor for the manufacture of medicaments

The invention relates the use of a cathepsin K inhibitor (CTKI) or CTK, a mutein, isoform, fused protein, functional derivative, active fraction, circularly permutated derivative, a salt or inducer thereof in the manufacture of a medicament for treating a disease in which SDF-1 activity and/or concentration is involved with the development and/or course of the disease.

Stem cells having increased sensitivity to sdf-1 and methods of generating and using same

The present invention relates to stem cells which exhibit increased sensitivity to a chemoattractant and, more particularly, to methods of generating and using them such as in clinical applications involving stem cell transplantation.

Chimeric mammals with human hematopoietic cells

L'invention concerne un mammifère chimérique ayant une greffe de moelle osseuse stable de cellules hématopoïétiques humaines capables d'effectuer une différentiation dans des lignées multiples de cellules matures humaines, au moins 30 % des cellules hématopoïétiques de la moelle osseuse du mammifère étant d'origine humaine. Le procédé de l'invention consiste à irradier de manière subléthale un mammifère immunodéficient, à introduire par perfusion les cellules hématopoïétiques humaines dans le mammifère et à administrer une quantité efficace d'un facteur de croissance de mastocytes humaines (MGF) et une protéine de fusion d'interleukine-3/facteur de stimulation d'une colonie de macrophages de granulocytes humains (GM-CSF/IL-3 FP) pour favoriser la greffe de cellules humaines dans la moelle osseuse de mammifères chimériques. The invention relates to a chimeric mammal having a stable bone marrow transplant of human hematopoietic cells capable of differentiating into multiple lines of mature human cells, at least 30% of the hematopoietic cells of the mammalian bone marrow being of origin. human. The method of the invention includes sublethally irradiating an immunodeficient mammal, infusing human hematopoietic cells into the mammal, and administering an effective amount of human mast cell growth factor (MGF) and a fusion protein. interleukin-3 / stimulating factor of a colony of macrophages of human granulocytes (GM-CSF / IL-3 FP) to promote the transplantation of human cells into the bone marrow of chimeric mammals.

Short beta-defensin-derived peptides

The invention is directed to beta-defensin-derived peptides and their use in modulating the activity of hematopoietic cells and other CXCR4-expressing cells. Specifically, the invention provides compositions and methods useful in the treatment of cancer. The invention further provides compositions and methods useful for promoting mobilization and transplantation of hematopoietic stem cells and progenitor cells.

Stem cells suitable for transplantation, their preparation and pharmaceutical compositions comprising them

The present invention relates to stem cells suitable for transplantation and to methods for their preparation.

The use of a protease or a protease inhibitor for the manufacture of medicaments

The invention relates the use of a cathepsin K inhibitor (CTKI) or CTK, a mutein, isoform, fused protein, functional derivative, active fraction, circularly permutated derivative, a salt or inducer thereof in the manufacture of a medicament for treating a disease in which SDF-1 activity and/or concentration is involved with the development and/or course of the disease.

Stem cells having increased sensitivity to sdf-1 and methods of generating and using same

The present invention relates to stem cells which exhibit increased sensitivity to a chemoattractant and, more particularly, to methods of generating and using them such as in clinical applications involving stem cell transplantation.

Chimeric sIL-6R / IL-6 protein, DNA, vector, cell, method of preparation as well as various uses of said protein

Catecholamine receptor modulation

Stem cells having increased sensitivity to a chemoattractant and methods of generating and using same

The present invention relates to stem cells which exhibit increased sensitivity to a chemoattractant and, more particularly, to methods of generating and using them such as in clinical applications involving stem cell transplantation.

Elastasehemmer bei leukämie

Χιμαιρικη πρωτεϊνη διαλυτου υποδοχεα/συνδετη ιντepλευκινης-6, αναλογα και αυτης και χρησεις αυτης

Παρέχονται χιμαιρικές πρωτεΐνες κατασκευασμένες από την σύντηξη της φυσικά απαντώμενης μορφής του διαλυτού υποδοχέα IL-6 και της IL-6 οι οποίες είναι χρήσιμες στην θεραπευτική αγωγή καρκίνου και ηπατικών ανωμαλιών, στην ενίσχυση μεταμόσχευσης μυελού οστών, και σε θεραπευτική αγωγή άλλων σχετιζόμενων με IL-6 καταστάσεων.

Chimäres lösliches interleukin-6 rezeptor/ligand protein, analoge und verwendungen

Stem cells having increased sensitivity to a chemoattractant and methods of generating and using same

Stem cells having increased sensitivity to a chemo-attractant and methods of generating and using same

Method of generating stem cells having increased sensitivity to a chemo-attractant

Elastase inhibitor in leukemia

The invention relates to the use of an elastase inhibitor in the manufacture of a medicament for the treatment of leukemia, preferably acute leukemia and more preferably for the treatment of AML

Use of an elastase inhibitor in the manufacture of a medicament for the treatment of leukemia

The invention relates to the use of an elastase inhibitor in the manufacture of a medicament for the treatment of leukemia, preferably acute leukemia and more preferably for the treatment of AML

Chimeric interleukin-6 soluble receptor/ligand protein analogs thereof and uses thereof

Inhibition of CXCR4 and/or cell motility by phenylalanine, cysteine or peptides containing said amino acids

Inhibition of cxcr4 and/or cell motility by phenylalanine, cysteine or peptides containing said aminoacids

The invention relates to phenylalanine, cysteine, derivatives of said amino acids, peptides comprising them, and to their use in diseases disorders or conditions whose pathology is caused by or associated with CXCR4 activity and/or cell motility.

Enzyminhibitor i leukemi

Oppfinnelsen angår anvendelse av en elastaseinhibitor til fremstilling av et medikament for behandling av leukemi, fortrirmsvis akutt leukemi og mer fortrirmsvis behandling av AML.

Migration of hematopoietic stem cells and progenitor cells to the liver

Migration of hematopoietic stem cells and progenitor cells to th e liver

The invention relates to transplantation of hematopoietic stem cells (HSC) and/or progenitor cells (HPC) into the liver. More specifically the invention relates to the use of chemokines, preferably SDF-1, for enhancing homing of HSC/HPC to the liver.

Migration of hematopoietic stem cells and progenitor cells to the liver