Tumor-specific immunity can be enhanced by transfection of tumor cells with syngeneic MHC-class-II genes or allogeneic MHC-class-I genes.
Mouse Sal sarcoma cells are lethal in the autologous A/J (KkDd) host. In order to improve the immune response to the Sal tumor, Sal cells have been transfected with syngeneic MHC-class-II or allogeneic MHC-class-I genes. MHC-class-II transfectants are uniformly rejected by the autologous host and immunization with them protects against subsequent Sal challenge. The improved immunity is probably the result of enhanced generation of tumor-specific Th cells. We hypothesize that class-II tumor cells trigger an improved Th-cell response because they directly present Sal tumor antigens in the context of class-II molecules to Th cells, by-passing professional APC. Studies by others have demonstrated that antigen presentation requires an intracellular signal transmitted by the cytoplasmic domain of the APC class-II molecule. Sal cells expressing class-II antigens with truncated cytoplasmic domains are as malignant as wild-type Sal cells. These experiments therefore support the role of tumor-cell class-II molecules as antigen presentation elements, and demonstrate the requirement for intact class-II molecules for tumor protection. Sal cells have also been transfected with allogeneic MHC-class-I genes. Although Kb-transfected cells are not rejected by A/J mice, Db-transfected Sal cells and Kb- plus Db-transfected cells are rejected. The Db transfectants effectively immunize A/J mice against subsequent Sal challenge. These experiments demonstrate that expression of certain allogeneic MHC-class-I genes can lead to tumor-specific immunity, and that such transfectants can protect against challenges of wild-type tumor cells. Transfection of tumor cells with syngeneic MHC-class-II or allogeneic MHC-class-I genes may therefore be a potential strategy for improving tumor-specific immunity in the autologous host.
Ostrand-Rosenberg
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Department of Biological Sciences, University of Maryland Baltimore County 21228.
Roby
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Clements
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Cole
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D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006084:Graft Rejection; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D051379:Mice; D008805:Mice, Inbred A; D008954:Models, Biological; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II