Materials and methods for treating oncological disease

Abstract

Novel methods are disclosed for treating oncological disorders in an individual or animal using a superantigen expressed in tumor cells. A gene encoding a superantigen, such as an M-like protein of group A streptococci, can be introduced into a tumor cell in order to make the tumor cell more immunogenic in the host. Also contemplated are methods wherein a cell expresses a superantigen or superantigens, and immunogenic or immunostimulatory proteins, such as foreign MHC, cytokines, porcine-derived hyperacute rejection antigen, Mycobacterium-derived antigens, and the like. The subject invention also pertains to cells transformed with polynucleotides encoding a superantigen and foreign MHC antigen, cytokines, and other immunogenic or immunostimulatory proteins. Transformed cells according to the subject invention are then provided to an individual or animal in need of treatment for an oncological disorder. The immune response to tumor cells transformed according to the present invention inhibits in vivo tumor growth and results in subsequent tumor regression. The subject invention also pertains to cell lines transformed with genes encoding a superantigen and, optionally, a foreign Class II MHC antigen and/or a cytokine.

1 . A method for preventing or treating an oncological disease in a human or domesticated animal, said method comprising introducing a polynucleotide coding for a superantigen into a cell, wherein said superantigen is expressed by said cell, and providing said transformed cells to said human or animal, and wherein said superantigen comprises an M-like protein.  
     
     
         2 . The method according to  claim 1 , wherein said M-like protein is the emmL-55 protein, or a fragment or variant thereof.  
     
     
         3 . The method according to  claim 1 , said method further comprising use of a traditional therapeutic treatment to treat said oncological disorder.  
     
     
         4 . The method according to  claim 3 , wherein said therapy is selected from the group consisting of surgical resection of a tumor, radiotherapy, chemotherapy, and antibody-directed antitumor therapy.  
     
     
         5 . The method according to  claim 1 , wherein said method further comprises the use of a dendritic cell cancer vaccine.  
     
     
         6 . The method according to  claim 1 , wherein said cells are transformed in vivo in said human or animal.  
     
     
         7 . The method according to  claim 1 , wherein said cells are transformed in vitro.  
     
     
         8 . The method according to  claim 1 , wherein the oncological disorder to be treated is selected from the group consisting of lynphomas, leukemias, carcinomas, sarcomas, brain tumors, gliomas, glioblastomas, neuroblastomas, melanomas, hepatomas, medulloblastomas and Wilm's tumors.  
     
     
         9 . The method according to  claim 1 , wherein said polynucleotide coding for said superantigen is introduced into said cell using a delivery vector selected from the group consisting of adenovirus, adeno-associated virus, retrovirus, pox virus, herpes virus, plasmids, double-stranded nucleic acid and single-stranded nucleic acid.  
     
     
         10 . The method according to  claim 1 , wherein said polynucleotide coding for said superantigen is introduced into said cell using a liposome comprising said polynucleotide.  
     
     
         11 . A method for preventing or treating an oncological disease in a human or domesticated animal, said method comprising introducing a polynucleotide coding for a first superantigen into a cell, and further introducing into said cell a second polynucleotide coding for at least one viral, bacterial or eukaryotic protein that is immunogenic or immunostimulatory, wherein said first superantigen and said viral, bacterial or eukaryotic protein is expressed by said cell, and providing said transformed cells to said human or animal, and wherein superantigen comprises an M-like protein.  
     
     
         12 . The method according to  claim 11 , wherein said bacterial or eukaryotic protein is selected from the group consisting of foreign MHC antigens, cytokines, Mycobacterium-derived antigens, porcine-derived hyperacute rejection antigens, and a second superantigen.  
     
     
         13 . The method according to  claim 11 , wherein said M-like protein is the emmL-55 protein, or a fragment or variant thereof.  
     
     
         14 . The method according to  claim 11 , said method further comprising use of a traditional therapeutic treatment to treat said oncological disorder.  
     
     
         15 . The method according to  claim 14 , wherein said therapy is selected from the group consisting of surgical resection of a tumor, radiotherapy, chemotherapy, and antibody-directed antitumor therapy.  
     
     
         16 . The method according to  claim 11 , wherein said method further comprises the use of a dendritic cell cancer vaccine.  
     
     
         17 . The method according to  claim 11 , wherein said cells are transformed in vivo in said human or animal.  
     
     
         18 . The method according to  claim 11 , wherein said cells are transformed in vitro.  
     
     
         19 . The method according to  claim 11 , wherein the oncological disorder to be treated is selected from the group consisting of lymphomas, leukemias, carcinomas, sarcomas, brain tumors, gliomas, glioblastomas, neuroblastomas, melanomas, hepatomas, medulloblastomas and Wilm's tumors.  
     
     
         20 . The method according to  claim 11 , wherein said polynucleotide coding for said superantigen and/or said polynucleotide coding for said viral, bacterial or eukaryotic protein is introduced into said cell using a delivery vector selected from the group consisting of adenovirus, adeno-associated virus, retrovirus, pox virus, herpes virus, plasmids, double-stranded nucleic acid and single-stranded nucleic acid.  
     
     
         21 . The method according to  claim 11 , wherein said polynucleotide coding for said superantigen and/or said polynucleotide coding for said viral, bacterial or eukaryotic protein is introduced into said cell using a liposome comprising said polynucleotide.  
     
     
         22 . The method according to  claim 12 , wherein said cytokine is selected from the group consisting of IL-1, IL-2, IL-3, IL-4, TNFα, IFNα, IFNβ, IFNγ, GM-CSF, MIP1α, MIP1γ and TGFγ.  
     
     
         23 . The method according to  claim 12 , wherein said foreign MHC antigen is selected from the group consisting of class I, class II and class III.  
     
     
         24 . A polynucleotide molecule, wherein said polynucleotide molecule comprises a nucleotide sequence encoding an M-like protein and a nucleotide sequence encoding a foreign MHC antigen.  
     
     
         25 . A cell transformed with a polynucleotide molecule, wherein said polynucleotide molecule comprises a nucleotide sequence encoding an M-like protein and a nucleotide sequence encoding a foreign MHC antigen.