The bacterial superantigen staphylococcal enterotoxin A (SEA) is an extremely potent activator of T lymphocytes when presented on MHC class II antigens. In order to induce T lymphocytes to reject a tumor, we substituted the specificity of SEA for MHC class II molecules with specificity for tumor cells by combining SEA with a MAb recognizing colon carcinomas. Chemical conjugates or recombinant fusion proteins of the MAb C215 and SEA retained excellent antigen binding properties whereas the binding to MHC class II was markedly reduced. The hybrid proteins directed SEA responsive T cells to tumors with specificity determined by the specificity of the MAb. Significant tumor cell killing was obtained at picomolar concentrations of the hybrid proteins and was the result of direct cell mediated by cytotoxicity as well as production of tumoricidal cytokines by T cells. Targeting of superantigens represents a novel approach to specific immunomodulation and deserves further study as a potential therapy for malignant disease.
Index Entries:Monoclonal antibodies SEA superantigen T lymphocyte colon cancer
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- 1.Houghton, A.N. and Scheinberg, D.S. (1991). Monoclonal antibodies inComprehensive Textbook of Oncology (Moosa, A. K., Schimpff, C., and Robson, M. C., eds.), Williams and Wilkins, Baltimore, MD., p. 601.Google Scholar
- 2.Brown, S. L., Miller, R. A., and Levy, R. (1989). Anti-idiotype antibody therapy of B cell lymphoma.Sem. Oncol. 16, 199–210.Google Scholar
- 4.Harris, D. T. and Mastrangelo, M. J. (1989) Serotherapy of cancer.Sem. Oncol. 16, 180–198.Google Scholar
- 6.Gerlach, J. H. (1991) Development of drug and radiation resistance, inComprehensive Textbook of Oncology (Moosa, A. K., Schimpff, C., and Robson, M. C., eds.), Williams and Wilkins, Baltimore, MD, p. 143.Google Scholar
- 18.Kalland, T., Hedlund, G., Dohlsten, M., and lando, P. A. (1991) Staphylococcal enterotoxin-dependent cell-mediated cytotoxicity.Curr. Topics Microbiol. Immunol. 174, 81–92.Google Scholar
- 19.Herrman, T., Maryanski, J. L., Romero, P., Fleischer, B., and MacDonald, H. R. (1990) Activation of MHC class I restricted CD8+ CTL by microbial T cell mitogens. Dependence upon MHC class II expression of the target cells and Vß usage of the responder T cell.J. Immunol. 144, 1181–1186.Google Scholar
- 27.Dohlsten, M., Hedlund, G., Segrén, S., Lando, P. A., Herrman, T., Kelly, A. P., and Kalland, T. (1991) Human major histocompatibility complex class II-negative colon carcinoma cells present staphylococcal superantigens to cytotoxic T lymphocytes: evidence for a novel enterotoxin receptor.Eur. J. Immunol. 21, 1229–1235.PubMedCrossRefGoogle Scholar
- 28.Björk, P., Jönsson, U., Svedberg, H., Larsson, K., Lind, P., Hedlund, G., Dohlsten, M., and Kalland, T. (1993) Isolation, partial characterization and molecular cloning of a human colon adenocarcinoma cell surface glycoprotein recognized by the C215 mouse monoclonal antibody.J. Biol. Chem., in press.Google Scholar
- 30.Johnson, H. M., Stanton, G. J., and Baron, S. (1977) Relative ability of mitogens to stimulate production of interferon by lymphoid cells and to induce suppression of the in vitro immune response.Proc. Soc. Exp. Biol. Med. 154, 49–56.Google Scholar
- 32.Parsonnet, J. and Gillis, Z. A. (1988) Production of tumor necrosis factor by human monocytes in response to toxic shock syndrome toxin-1.J. Infect. Disease 158, 1026–1033.Google Scholar