Targeting of superantigens |
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Authors: | Terje Kalland Mikael Dohlsten Lars Abrahmsén Gunnar Hedlund Per Björk Peter A Lando Anette Sundstedt Eva Åkerblom Peter Lind |
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Institution: | 1. Kabi Pharmacia Oncology, Lund, Sweden 2. Department of Tumor Immunology, Lund University, Sweden 3. Kabi Pharmacia Bioscience Center, Stockholm, Sweden 4. Kabi Pharmacia Therapeutics, Uppsala, Sweden
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Abstract: | 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. |
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