Lipids as synthetic vectors to enhance antigen processing and presentation ex-vivo in dendritic cell therapy

The invention covers the use of certain classes of lipids including cationic lipids in ...

METHODS AND COMPOSITIONS COMPRISING CATIONIC LIPIDS FOR STIMULATING TYPE 1 INTERFERON GENES

Methods and compositions for modifying type I IFN signaling pathways in a subject comprising the administration a cationic lipid to the subject are provided. The cationic lipids comprise l,2-dioleoyl-3-trimethylammonium propane (DOTAP), N-l-(2,3-dioleoyloxy)-propyl- ?, ?, ?-trimethyl ammonium chloride (DOTMA), l,2-dioleoyl-sn-glycero-3- ethylphosphocholine (DOEPC), enantiomers and combinations thereof. The compositions may further comprise one or more antigenic components, wherein such components are autologous or nonautologous.

Novel hpv16 non hla-restricted t-cell vaccines, compositions and methods of use thereof

Novel HPV16 non HLA-restricted T-cell vaccines, compositions and methods of use thereof

Novel human papillomovirus immunogenic compositions and methods of use thereof are provided. The compositions comprise unique combinations of multi-epitope peptide sequences specifically selected and designed to be effectively processed and cross-presented to T-cells. The peptides utilized in the compositions display high levels of binding with HLA-supertypes. The immunogenic compositions are broadly applicable to large proportions of target populations. The compositions comprise adjuvants such as cationic lipids.

LIPIDS AS SYNTHETIC VECTORS TO ENHANCE ANTIGEN PROCESSING AND PRESENTATION EX-VIVO IN DENDRITIC CELL THERAPY

The invention covers the use of certain classes of lipids including cationic lipids in ex-vivo dendritic cell therapies. The cationic lipids enhance antigen uptake, processing and presentation of the processed antigens by dendritic cells to CD8+ and CD4+ T-cells via the MHC classes I and II presentation pathways respectively. Antigen uptake via cationic lipid by dendritic cells result in significant lowering of the population of the immune suppressive regulatory T cells in the tumors and a significant increase of the tumor targeting cytotoxic T-cells. Loss of regulatory T cells and increase of tumor specific cytotoxic cells are conducive to effective elimination of the tumors.

Novel HPV16 non HLA-restricted T-cell vaccines, compositions and methods of use thereof

Novel human papillomovirus immunogenic compositions and methods of use thereof are provided. The compositions comprise unique combinations ofmulti-epitope peptide sequences specifically selected and designed to be effectively processed and cross-presented to T-cells. The peptides utilized in the compositions display high levels of binding with HLA-supertypes. The immunogenic compositions are broadly applicable to large proportions of target populations. The compositions comprise adjuvants such as cationic lipids.

NOVEL HPV16 NON HLA-RESTRICTED T-CELL VACCINES, COMPOSITIONS AND METHODS OF USE THEREOF

Novel human papillomovirus immunogenic compositions and methods of use thereof are provided. The compositions comprise unique combinations of multi-epitope peptide sequences specifically selected and designed to be effectively processed and cross-presented to T-cells. The peptides utilized in the compositions display high levels of binding with HLA-supertypes. The immunogenic compositions are broadly applicable to large proportions of target populations. The compositions comprise adjuvants such as cationic lipids.

NOVEL HPV16 NON HLA-RESTRICTED T-CELL VACCINES, COMPOSITIONS AND METHODS OF USE THEREOF

International Patent Classification: A61K 38/00 (2006.01) C07K 14/00 (2006.01) A61K 39/12 (2006.01) A61K 9/127 (2006.01) A61K 39/00 (2006.01) (21) International Application Number: (22) International Filing Date: PCT/US2017/055119 1218k9 OStim # # I _r_71111M 11 s-7 ,• (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date 12 April 2018 (12.04.2018) WIPO I PCT ill~~~~~~~~ 011101010VIIIOH olo omoiloo Em Eno iflo oimIE (10) International Publication Number WO 2018/067689 Al 04 October 2017 (04.10.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/404,458 05 October 2016 (05.10.2016) US (71) Applicant: PDS BIOTECHNOLOGY CORPO- RATION [US/US]; 675 US Highway 1, North Brunswick, NJ 08902 (US). (72) Inventors: BEDU-ADDO, Frank; 24 Tamar Lane, Stam- ford, CT 06905 (US). CONN, Greg; Orense 17, Esc. Dcha. 4 Dcha., 28020 Madrid ...

Lipids as synthetic vectors to enhance antigen processing and presentation

The invention covers the use of certain classes of lipids including cationic lipids in ...

Methods and compositions comprising cationic lipids for stimulating type 1 interferon genes

Methods and compositions for modifying type I IFN signaling pathways in a subject comprising the administration a cationic lipid to the subject are provided. The cationic lipids comprise l,2-dioleoyl-3-trimethylammonium propane (DOTAP), N-l-(2,3-dioleoyloxy)-propyl- Ν, Ν, Ν-trimethyl ammonium chloride (DOTMA), l,2-dioleoyl-sn-glycero-3- ethylphosphocholine (DOEPC), enantiomers and combinations thereof. The compositions may further comprise one or more antigenic components, wherein such components are autologous or nonautologous.

METHODS AND COMPOSITIONS COMPRISING CATIONIC LIPIDS FOR STIMULATING TYPE 1 INTERFERON GENES

Methods and compositions for modifying type I IFN signaling pathways in a subject comprising the administration a cationic lipid to the subject are provided. The cationic lipids comprise 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), N-1-(2,3-dioleoyloxy)-propyl-N,N,N-trimethyl ammonium chloride (DOTMA), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC), enantiomers and combinations thereof. The compositions may further comprise one or more antigenic components, wherein such components are autologous or nonautologous. 1. A method for modifying a type I IFN signaling pathway in a subject comprising the administration a cationic lipid to the mammal.2. The method of claim 1 , wherein the cationic lipid comprises 1 claim 1 ,2-dioleoyl-3-trimethylammonium propane (DOTAP) claim 1 , N-1-(2 claim 1 ,3-dioleoyloxy)-propyl-N claim 1 ,N claim 1 ,N-trimethyl ammonium chloride (DOTMA) claim 1 , 1 claim 1 ,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC) claim 1 , and combinations thereof.3. The method of claim 2 , wherein the cationic lipid comprises an enantiomer of the cationic lipid.4. The method of claim 3 , wherein the wherein the cationic lipid is 1 claim 3 ,2-dioleoyl-3-trimethylammonium propane (DOTAP).5. The method of claim 4 , wherein the enantiomer is (R)-1 claim 4 ,2-dioleoyl-3-trimethylammonium propane (R-DOTAP) or (S)-1 claim 4 ,2-dioleoyl-3-trimethylammonium propane (S-DOTAP).6. The method of claim 1 , wherein the type I IFN signaling pathway is upregulated/activated.7. The method of claim 1 , wherein the type I IFN signaling pathway is down-regulated/deactivated.8. The method of claim 6 , wherein the cationic lipid comprises 1 claim 6 ,2-dioleoyl-3-trimethylammonium propane (DOTAP) claim 6 , N-1-(2 claim 6 ,3-dioleoyloxy)-propyl-N claim 6 ,N claim 6 ,N-trimethyl ammonium chloride (DOTMA) claim 6 , 1 claim 6 ,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC) claim 6 , and combinations thereof.9. The method of claim 6 , wherein the cationic lipid ...

Methods and compositions comprising cationic lipids for stimulating type I interferon genes

Methods and compositions for modifying type I IFN signaling pathways in a subject comprising the administration a cationic lipid to the subject are provided. The cationic lipids comprise 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), N-1-(2,3-dioleoyloxy)-propyl-N,N,N-trimethyl ammonium chloride (DOTMA), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC), enantiomers and combinations thereof. The compositions may further comprise one or more antigenic components, wherein such components are autologous or nonautologous.

LIPIDS AS SYNTHETIC VECTORS TO ENHANCE ANTIGEN PROCESSING AND PRESENTATION EX-VIVO IN DENDRITIC CELL THERAPY

The invention covers the use of certain classes of lipids including cationic lipids in ex-vivo dendritic cell therapies. The cationic lipids enhance antigen uptake, processing and presentation of the processed antigens by dendritic cells to CD8+ and CD4+ T-cells via the MHC classes I and II presentation pathways respectively. Antigen uptake via cationic lipid by dendritic cells result in significant lowering of the population of the immune suppressive regulatory T cells in the tumors and a significant increase of the tumor targeting cytotoxic T-cells. Loss of regulatory T cells and increase of tumor specific cytotoxic cells are conducive to effective elimination of the tumors.

LIPIDS AS SYNTHETIC VECTORS TO ENHANCE ANTIGEN PROCESSING AND PRESENTATION EX-VIVO IN DENDRITIC CELL THERAPY

The invention covers the use of certain classes of lipids including cationic lipids in ex-vivo dendritic cell therapies. The cationic lipids enhance antigen uptake, processing and presentation of the processed antigens by dendritic cells to CD8+and CD4+T-cells via the MHC classes I and II presentation pathways respectively. Antigen uptake via cationic lipid by dendritic cells result in significant lowering of the population of the immune suppressive regulatory T cells in the tumors and a significant increase of the tumor targeting cytotoxic T-cells. Loss of regulatory T cells and increase of tumor specific cytotoxic cells are conducive to effective elimination of the tumors.

NOVEL HPV16 NON HLA-RESTRICTED T-CELL VACCINES, COMPOSITIONS AND METHODS OF USE THEREOF

Novel human papillomovirus immunogenic compositions and methods of use thereof are provided. The compositions comprise unique combinations of multi-epitope peptide sequences specifically selected and designed to be effectively processed and cross-presented to T-cells. The peptides utilized in the compositions display high levels of binding with HLA-supertypes. The immunogenic compositions are broadly applicable to large proportions of target populations. The compositions comprise adjuvants such as cationic lipids. 1. A composition comprising HPV peptide sequences , wherein the HPV peptide sequences correspond to HPV16 E6 peptides , and/or HPV16 E7 peptides and wherein the peptide sequences have a binding affinity of approximately IC50 of 5 ,000 nM with 5 HLA supertypes , and wherein some of the peptides are multi-epitope peptides.2. The composition of claim 1 , wherein the peptides comprise SEQ ID NOS: 5 claim 1 , 9 claim 1 , 10 and 11 claim 1 , or their lipidated versions consisting of SEQ ID NOS: 23 claim 1 , 24 claim 1 , 25 and 26.3. The composition of claim 2 , wherein the peptides are present in the composition as individual peptides.4. The composition of claim 2 , wherein the peptides are conjugated to each other either with a spacer or without a spacer to form a single long peptide encompassing the claimed sequences.5. The composition of claim 1 , further comprising an adjuvant.6. The composition of claim 5 , wherein the adjuvant consists of a cationic lipid.7. The composition of claim 6 , wherein the cationic lipid consists of DOTAP claim 6 , DDA claim 6 , DOEPC claim 6 , DOTMA claim 6 , R-DOTAP claim 6 , R-DDA claim 6 , R-DOEPC claim 6 , R-DOTMA claim 6 , S-DOTAP claim 6 , S-DDA claim 6 , S-DOEPC claim 6 , S-DOTMA claim 6 , variations or analogs thereof.8. The composition of claim 1 , wherein the HLA supertypes consist of HLA-A*02:01 claim 1 , HLA-A*03:01 claim 1 , HLA-A*24:02 claim 1 , HLA-B*07:02 claim 1 , and HLA-B*58:01.9. The composition of claim 1 , ...

METHODS TO ALTER THE TUMOR MICROENVIRONMENT FOR EFFECTIVE CANCER IMMUNOTHERAPY

Methods and compositions for altering the microenvironment of a tumor are provided. The methods comprise reducing the population of tumor-residing immune suppressive regulatory T-cells, increasing the population of tumor lysing T-cells (such as CD8+ T-cells) and improving the efficacy of cancer immunotherapy. The compositions comprise the use of cationic lipids optionally combined with autologous antigens, non-autologous antigens, or tumor-associated antigens. 1. A method for altering a tumor microenvironment comprising administering to a subject having a tumor , a composition comprising a cationic lipid.2. The method of claim 1 , further comprising autologous antigens claim 1 , non-autologous antigens claim 1 , or tumor-associated antigens.3. The method of claim 1 , wherein altering the tumor microenvironment comprises reducing the population of Tregs.4. The method of claim 1 , wherein altering the tumor microenvironment comprises both reducing the population of Tregs and increasing the population of CD8+ T-cells.5. The method of claim 1 , wherein altering the tumor microenvironment comprises reducing the Treg to CD8+ T-cell ratio.6. The method of claim 1 , wherein the composition further comprises an adjuvant or an agent that combats tumor immune suppression.7. The method of claim 6 , further comprising a T-cell activating vaccine.8. The method of claim 2 , wherein the composition further comprises DNA-based antigens claim 2 , RNA-based antigen claim 2 , growth factors claim 2 , GM-CSF claim 2 , cytokines claim 2 , synthetic peptides claim 2 , recombinant proteins claim 2 , or epitopes from one or more tumor-associated antigens.9. The method of claim 1 , wherein the cationic lipid is selected from the group consisting of DOTAP claim 1 , R-DOTAP claim 1 , S-DOTAP claim 1 , DOTMA claim 1 , R-DOTMA claim 1 , S-DOTMA claim 1 , DOEPC claim 1 , R-DOEPC claim 1 , and S-DOEPC.10. The method of claim 3 , wherein the cationic lipid consists of R-DOTAP and wherein the ...

LIPIDS AS SYNTHETIC VECTORS TO ENHANCE ANTIGEN PROCESSING AND PRESENTATION EX-VIVO IN DENDRITIC CELL THERAPY

The invention covers the use of certain classes of lipids including cationic lipids in ex-vivo dendritic cell therapies. The cationic lipids enhance antigen uptake, processing and presentation of the processed antigens by dendritic cells to CD8+and CD4+T-cells via the MHC classes I and II presentation pathways respectively. Antigen uptake via cationic lipid by dendritic cells result in significant lowering of the population of the immune suppressive regulatory T cells in the tumors and a significant increase of the tumor targeting cytotoxic T-cells. Loss of regulatory T cells and increase of tumor specific cytotoxic cells are conducive to effective elimination of the tumors. 1. An immunotherapy composition comprising at least one cationic lipid and at least one type of T-cell , wherein the at least one cationic lipid and at least one type of T-cell may be administered in combination or separately.2. The composition of where the T-cell comprises an antigen specific T-cell.3. The composition of where the T-cell comprises an adoptively transferred T-cell.4. The composition of where the T-cell comprises an autologous T-cell.5. The composition of where the T-cell comprises a CD4+ T-cell.6. The composition of where the T-cell comprises a CD8+ T-cell.7. The composition of where the cationic lipid comprises DOTAP claim 1 , DDA claim 1 , DOTMA or DOEPC claim 1 , and combinations thereof.8. A method of treating or preventing a disease claim 1 , comprising the administration of a composition to a subject in need thereof claim 1 , wherein the composition comprises at least one cationic lipid and at least one type of T-cell claim 1 , wherein the at least one cationic lipid and at least one type of T-cell may be administered in combination or separately.9. The composition of claim 8 , wherein the T-cells comprise adoptively transferred T-cells.10. The method of claim 8 , resulting in the priming and boosting of the adoptively transferred T-cells.11. The method of claim 8 , where ...

Methods and compositions comprising cationic lipids for stimulating type 1 interferon genes

Novel hpv16 non hla-restricted t-cell vaccines, compositions and methods of use thereof

methods and compositions comprising cationic lipids to stimulate type i interferon genes

Métodos e composições para modificar as vias de sinalização de IFN tipo I em um indivíduo compreendendo a administração de um lipídeo catiônico ao indivíduo são fornecidos. Os lipídeos catiônicos compreendem 1,2-dioleoil-3-trimetilamônio propano (DOTAP), cloreto de N-1-(2,3-dioleoilóxi)-propil-N,N,N-trimetil amônio (DOTMA), 1,2-dioleoil-sn-glicero-3-etilfosfocolina (DOEPC), enantiômeros e suas combinações. As composições podem ainda compreender um ou mais componentes antigênicos, em que esses componentes são autólogos ou não autólogos. Methods and compositions for modifying IFN type I signaling pathways in an individual comprising administering a cationic lipid to the individual are provided. The cationic lipids comprise 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), N-1- (2,3-dioleoyloxy) -propyl-N, N, N-trimethyl ammonium chloride (DOTMA), 1,2- dioleoil-sn-glicero-3-ethylphosfocolina (DOEPC), enantiomers and their combinations. The compositions can further comprise one or more antigenic components, where those components are autologous or non-autologous.

Lipids as synthetic vectors to enhance antigen processing and presentation ex-vivo in dendritic cell therapy

The invention covers the use of certain classes of lipids including cationic lipids in

新規ｈｐｖ１６非ｈｌａ拘束性ｔ細胞ワクチン、その組成物及び使用方法

【課題】新規ヒトパピローマウイルス免疫原性組成物及びその使用が提供される。【解決手段】前記組成物は、効果的に加工され、T細胞に交差提示されるように特に選択され、設計されたマルチエピトープペプチド配列の独特の組み合わせを含む。前記組成物に利用されるペプチドは、HLAスーパータイプとの高いレベルの結合を示す。前記免疫原性組成物は、大部分の標的集団に広く適用可能である。前記組成物は、カチオン性脂質等のアジュバントを含む。【選択図】図１

樹状細胞療法においてｅｘ ｖｉｖｏでの抗原のプロセシングと提示を亢進させるための合成ベクターとしての脂質

【課題】癌を治療するための組成物を提供する。【解決手段】養子移入されたＴ細胞のｉｎ ｖｉｖｏでの増殖を引き起こすことによって癌を治療するための組成物であって、カチオン性脂質、および養子移入されるＴ細胞を含む、組成物である。前記カチオン性脂質はＲ－ＤＯＴＡＰを含むことが好ましく、前記Ｔ細胞はＣＤ４＋Ｔ細胞またはＣＤ８＋Ｔ細胞であることが好ましい。【選択図】なし

Lipids as synthetic vectors to enhance antigen processing and presentation ex-vivo in dendritic cell therapy

The invention covers the use of certain classes of lipids including cationic lipids in ex-vivo dendritic cell therapies. The cationic lipids enhance antigen uptake, processing and presentation of the processed antigens by dendritic cells to CD8+ and CD4+ T-cells via the MHC classes I and II presentation pathways respectively. Antigen uptake via cationic lipid by dendritic cells result in significant lowering of the population of the immune suppressive regulatory T cells in the tumors and a significant increase of the tumor targeting cytotoxic T-cells. Loss of regulatory T cells and increase of tumor specific cytotoxic cells are conducive to effective elimination of the tumors.

Lipids as synthetic vectors to enhance antigen processing and presentation ex-vivo in dendritic cell therapy

The invention covers the use of certain classes of lipids including cationic lipids in ex-vivo dendritic cell therapies. The cationic lipids enhance antigen uptake, processing and presentation of the processed antigens by dendritic cells to CD8+ and CD4+ T-cells via the MHC classes I and II presentation pathways respectively. Antigen uptake via cationic lipid by dendritic cells result in significant lowering of the population of the immune suppressive regulatory T cells in the tumors and a significant increase of the tumor targeting cytotoxic T-cells. Loss of regulatory T cells and increase of tumor specific cytotoxic cells are conducive to effective elimination of the tumors.

Novel HPV16 non HLA-restricted T-cell vaccines, compositions and methods of use thereof

Novel human papillomovirus immunogenic compositions and methods of use thereof are provided. The compositions comprise unique combinations ofmulti-epitope peptide sequences specifically selected and designed to be effectively processed and cross-presented to T-cells. The peptides utilized in the compositions display high levels of binding with HLA-supertypes. The immunogenic compositions are broadly applicable to large proportions of target populations. The compositions comprise adjuvants such as cationic lipids.