A novel method for modification of tumor cells with bacterial superantigen with a heterobifunctional cross-linking agent in immunotherapy of cancer.
Bacterial superantigens (SAGs) bind to cognate Vbeta elements of T-cell receptors on T-cells and to major histocompatibility complex (MHC) class II molecules on antigen-presenting cells to activate T-cell subsets expressing the Vbeta elements. We examined the possibility that the direct binding of SAGs (staphylococcal enterotoxins B [SEB] and A [SEA]) to tumor cells decreases the toxicity of SAGs, and that antitumor immunity can be induced with the aid of T-helper-1 (Th1)-type cytokines and monokines released from T-cells and monocytes, respectively, by activation with SAGs. In this context, we have developed a general method for conjugating SEB and SEA directly to tumor cells with a heterobifunctional cross linking agent, N-(gamma- maleimidobutyryloxy) sulfosuccinimide sodium salt. Using this method, we have succeeded in conjugating SEB to a sufficient extent as to induce strong tumor immunity. Both in vitro T-cell culture with SEB-bearing Meth A cells and in vivo immunization with SEB-bearing Meth A cells induce strong antitumor activity. These results suggest that the direct conjugation of SAGs including SEB and SEA to tumor cells is a powerful and useful method for immunotherapy of cancer.
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques / Q000379:methods; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003602:Cytotoxicity, Immunologic / Q000276:immunology / Q000502:physiology; D004768:Enterotoxins / Q000737:chemistry / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology; D006207:Half-Life; D007167:Immunotherapy / Q000379:methods*; D016233:Immunotherapy, Active / Q000379:methods; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016685:Mitomycin / Q000494:pharmacology; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013438:Sulfhydryl Compounds / Q000737:chemistry; D018089:Superantigens / Q000737:chemistry* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology
D000906:Antibodies; D019496:Cancer Vaccines; D003432:Cross-Linking Reagents; D004768:Enterotoxins; D013438:Sulfhydryl Compounds; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D016685:Mitomycin