Autologous cancer cell vaccine

Abstract

An autologous cancer cell vaccine comprises cancer cells that express both MHCI and MHCII on their cell surface. The MHCI presents a cancer antigen and the MHCII presents a non-self antigen.

What is claimed is: 
     
         1 . A method for making isolated immunogenic cancer cells or an immunogenic extract thereof comprising both MHCI and MHCII, the method comprising:
 inducing expression of MHCII on cancer cells isolated from a subject;   incubating the cancer cells with a non-self antigen so that the non-self antigen will be bound to expressed MHCII; and   killing the cancer cells.   
     
     
         2 . The method of  claim 1 , further comprising identifying MHCII-positive cells after MHCII induction. 
     
     
         3 . The method of  claim 2 , further comprising separating the MHCII-positive cancer cells from MHCII-negative cancer cells to obtain a purified composition containing the MHCII-positive cells. 
     
     
         4 . The method of  claim 1 , further comprising isolating the cancer cells from a subject during a biopsy procedure or during surgical removal of a tumour. 
     
     
         5 . The method of  claim 1 , further comprising cryo-preserving the cancer cells. 
     
     
         6 . The method of  claim 1 , wherein the cells are killed by lethal irradiation, freezing and thawing in the absence of a cryo-preservation agent, or treatment with a cytotoxic compound. 
     
     
         7 . The method of  claim 1 , wherein the MHCII is induced on the cancer cells using an MHCII-inducing agent. 
     
     
         8 . The method of  claim 7 , wherein the MHCII-inducing agent is a cytokine, an MHCII expression construct or an MHCII-expressing cell that will fuse with the cancer cells. 
     
     
         9 . The method of  claim 8 , wherein the cytokine is IFN-α, IFN-β, IFN-γ, IL-4, IL-13, IL-23, TNF-α, or a combination thereof. 
     
     
         10 . The method of  claim 1 , wherein the non-self antigen is a non-human antigen. 
     
     
         11 . The method of  claim 10 , wherein said non-self antigen is selected from thyroglobulin, β-galactosidase, dextran, polylysine, tuberculin derived protein, ovalbumin (OVA), serum albumins such as bovine serum albumin (BSA), sheep serum albumin, goat serum albumins, or fish serum albumin, and keyhole limpet hemocyanin (KLH), and a combination thereof. 
     
     
         12 . The method of  claim 1 , wherein said non-self antigen is not a bovine antigen. 
     
     
         13 . The method of  claim 12 , wherein said non-self antigen is not BSA. 
     
     
         14 . The method of  claim 1 , wherein said inducing step is in a medium free of BSA. 
     
     
         15 . Isolated immunogenic cancer cells that express both MHCI and MHCII on their cell surface or an immunogenic extract thereof comprising both MHCI and MHCII, wherein a cancer antigen is bound to said MHCI and a non-self antigen is bound to said MHCII. 
     
     
         16 . The cells of  claim 15 , wherein the non-self antigen is a non-human antigen. 
     
     
         17 . The cells of  claim 16 , wherein said non-self antigen is selected from thyroglobulin, β-galactosidase, dextran, polylysine, tuberculin derived protein, ovalbumin (OVA), serum albumins such as bovine serum albumin (BSA), sheep serum albumin, goat serum albumins, or fish serum albumin, and keyhole limpet hemocyanin (KLH), and a combination thereof. 
     
     
         18 . The cells of  claim 15 , wherein said non-self antigen is not a bovine antigen. 
     
     
         19 . The cells of  claim 18 , wherein said non-self antigen is not BSA. 
     
     
         20 . An immunogenic composition comprising the isolated immunogenic cancer cells or immunogenic extract thereof of  claim 15  together with at least one excipient, carrier, buffer, stabilizer, or a combination thereof. 
     
     
         21 . The composition of  claim 20 , comprising from about 5% to about 100% MHCII-positive cancer cells, based on the total number of cells in the composition. 
     
     
         22 . The composition of  claim 21 , comprising at least about 50%, 90%, or 99% MHCII-positive cancer cells. 
     
     
         23 . An autologous cancer vaccine comprising the isolated immunogenic cancer cells or immunogenic extract thereof of  claim 15  together with at least one adjuvant. 
     
     
         24 . The vaccine of  claim 23 , wherein the adjuvant is selected from monophosphoryl Lipid A/synthetic trehalose dicorynomycolate (MPL-TDM), AS021/AS02, nonionic block co-polymer adjuvants, CRL 1005, aluminum phosphates, AIPO4), R-848, imiquimod, PAM3CYS, poly (I:C), loxoribine, bacille Calmette-Guerin (BCG),  Corynebacterium parvum , CpG oligodeoxynucleotides (ODN), cholera toxin derived antigens, CTA 1-DD, lipopolysaccharide adjuvants, complete Freund's adjuvant, incomplete Freund's adjuvant, saponin, mineral gels, aluminum hydroxide, surface active substances, lysolecithin, pluronic polyols, polyanions, peptides, oil or hydrocarbon emulsions in water, MF59, Montanide ISA 720, keyhole limpet hemocyanins (KLH), dinitrophenol, and combinations thereof. 
     
     
         25 . The vaccine of  claim 24 , comprising from about 5% to about 100% MHCII-positive cancer cells, based on the total number of cells in the vaccine. 
     
     
         26 . The vaccine of  claim 25 , comprising at least about 50%, 90%, or 99% MHCII-positive cancer cells. 
     
     
         27 . The vaccine of  claim 24 , provided in divided doses for multiple inoculations. 
     
     
         28 . The vaccine of  claim 27 , provided in seven divided doses, wherein each dose comprises from about 1×10 4  to about 1×10 9  cancer cells. 
     
     
         29 . The vaccine of  claim 28 , wherein each dose comprises about 1×10 7  cancer cells.