Composition and therapeutic anti-tumour vaccine

Abstract

The invention relates to a composition which induces, in a host, a cytotoxic cell response directed against cells expressing an antigen, in particular tumour cells, and which comprises red blood cells containing said antigen. These red blood cells may be in the form of an immune complex with an immunoglobulin, in particular IgG, which recognizes an epitope at the surface of the red blood cells, and/or be heat-treated or chemically treated so as to promote phagocytosis of said red blood cells by dendritic cells. As a variant, the red blood cells may be xenogenic red blood cells. The invention also relates to a therapeutic especially anti-tumour vaccine containing such a composition.

1 - 37 . (canceled) 
     
     
         38 . A method for inducing an immune response against a tumour comprising administering to a patient in need thereof an effective amount of a composition comprising red blood cells containing a tumour antigen intracellularly. 
     
     
         39 . The method of  claim 38 , wherein the immune response is a cytotoxic cellular response against tumour cells or a tumour. 
     
     
         40 . The method of  claim 38 , wherein the composition is a vaccine composition. 
     
     
         41 . The method of  claim 38 , wherein the composition further comprises an adjuvant. 
     
     
         42 . The method of  claim 38 , wherein the red blood cells are in the form of an immune complex with an immunoglobulin which recognizes an epitope at the surface of the red blood cells, wherein the immune complex promotes phagocytosis of the red blood cells by antigen presenting cells (APCs). 
     
     
         43 . The method of  claim 42 , wherein the red blood cells form an immune complex with an anti-rhesus or anti-glycophorin A or anti-CR1 antibody. 
     
     
         44 . The method of  claim 42 , wherein the immunoglobulin is an IgG. 
     
     
         45 . The method of  claim 38 , wherein the red blood cells are heat-treated or chemically-treated, wherein the heat- or chemical-treatment promotes phagocytosis of the red blood cells by APCs. 
     
     
         46 . The method of  claim 42 , wherein the red blood cells in the form of an immune complex are heat-treated and/or chemically-treated. 
     
     
         47 . The method of  claim 38 , wherein the red blood cells are xenogenic red blood cells. 
     
     
         48 . The method of  claim 41 , wherein the adjuvant activates dendritic cell maturation. 
     
     
         49 . The method of  claim 41 , wherein the adjuvant is present in the red blood cells, at their surface and/or outside the red blood cells. 
     
     
         50 . The method of  claim 41 , wherein the adjuvant is a Toll-like receptor (TLR) ligand or a cytokine. 
     
     
         51 . The method of  claim 50 , wherein the TLR ligand is selected from imidazoquinolines selected from imidazoquinoline, imiquimod, resiquimod, CpG oligodeoxynucleotides LPSs (lipopolysaccharides) and poly(inosinic acid)-poly(cytidylic acid). 
     
     
         52 . The method of  claim 50 , wherein the cytokine is selected from interferon alpha (IFNα), interleukin 2 (IL-2), interferon gamma (IFNγ), Granulocyte Monocyte-Colony Stimulating Factor (GM-CSF), interleukin 12 (IL-12) and Tumor Necrosis Factor alpha (TNFα). 
     
     
         53 . The method of  claim 38 , wherein the red blood cells comprise at least two tumour antigens representative of the tumour to be treated. 
     
     
         54 . The method of  claim 38 , wherein the tumour antigen is selected from the group consisting of alpha-actinin-4; ARTC1; BCR-ABL fusion protein (b3a2); B-RAF; CASP-5; CASP-8; beta-catenin; Cdc27; CDK4; CDKN2A; COA-1; dek-can fusion protein; EFTUD2; Elongation factor 2; ETV6-AML1 fusion protein; FN1; GPNMB; LDLR-fucosyltransferaseAS fusion protein; HLA-A2d; HLA-A11d; hsp70-2; KIAAO205; MART2; ME1; MUM-If; MUM-2; MUM-3; neo-PAP; Myosin class I; NFYC; OGT; OS-9; pml-RARalpha fusion protein; PRDXS; PTPRK; K-ras; N-ras; RBAF600; SIRT2; SNRPD1; SYT-SSX1 or -SSX2 fusion protein; Thosephosphate Isomerase; BAGE-1; GAGE-1,2,8; GAGE-3,4,5,6,7; GnTVf; HERV-K-MEL; KK-LC-1; KM-HN-1; LAGE-1; MAGE-A1; MAGE-A2; MAGE-A3; MAGE-A4; MAGE-A6; MAGE-A9; MAGE-A10; MAGE-A12; MAGE-C2; mucin k; NA-88; NY-ESO-1/LAGE-2; SAGE; Sp17; SSX-2; SSX-4; TRAG-3; TRP2-INT2g; CEA; gp100/Pmel17; Kallikrein 4; mammaglobin-A; Melan-A/MART-1; NY-BR-1; OA1; PSA; RAB38/NY-MEL-1; TRP-1/gp75; TRP-2; tyrosinase; adipophilin; AIM-2; BING-4; CPSF; cyclin D1; Ep-CAM; EphA3; FGF5; G250/MN/CAIX; HER-2/neu; IL13Ralpha2; Intestinal carboxyl esterase; alpha-foetoprotein; M-CSF; mdm-2; MMP-2; MUC1; p53; PBF; PRAME; PSMA; RAGE-1; RNF43; RU2AS; secernin 1; SOX10; STEAP1; survivin; Telomerase; WT1; FLT3-ITD; BCLX(L); DKK1; ENAH(hMena); MCSP; RGSS; Gastrin-17; Human Chorionic Gonadotropin, EGFRvIII, HER2, HER2/neu, P501, Guanylyl Cyclase C, and PAP. 
     
     
         55 . The method of  claim 42 , wherein the APCs are dendritic cells. 
     
     
         56 . The method of  claim 55 , wherein the APCs comprise dendritic cells from spleen and/or liver. 
     
     
         57 . The method of  claim 45 , wherein the APCs are dendritic cells. 
     
     
         58 . The method of  claim 57 , wherein the APCs comprise dendritic cells from spleen and/or liver. 
     
     
         59 . The method of  claim 38 , wherein the red blood cells originate from a donor. 
     
     
         60 . The method of  claim 38 , wherein the red blood cells containing a tumour antigen intracellularly have been prepared by lysis in a dialysis element and resealing. 
     
     
         61 . The method of  claim 38 , wherein the red blood cells are administered intravenously by injection or infusion. 
     
     
         62 . The method of  claim 38 , wherein the red blood cells are administered as a suspension, wherein the suspension comprises a saline buffer comprising NaCl, adenine, glucose or mannitol.