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• W4313343457 endingPage "5313" @default.
• W4313343457 startingPage "5309" @default.
• W4313343457 abstract "Abstract The bacterial superantigen staphylococcal enterotoxin A (SEA) is a potent inducer of cytokine production and cytotoxic T cell responses. To target a T cell attack against tumor cells we have genetically engineered a fusion protein of SEA and the Fab part of the tumor-reactive mAb C215. Injection of this Fab-SEA fusion protein to mice carrying lung metastases of the poorly immunogenic B16 melanoma transfected with the C215 Ag resulted in infiltration of cytokine-producing T cells, perforin-containing CTL, and a marked tumor elimination. Fab-SEA therapy induced substantial levels of IFN-γ and TNF-α in serum. In the present study we have characterized the molecular mechanisms of the antitumor effect induced by Fab-SEA treatment in vivo. Neutralization of cytokines by specific Abs demonstrated a major role for IFN-γ in the suppression of tumor growth. In addition, a minor contribution of TNF-α was recorded. Injections of Fab-SEA into normal mice induced strong CTL activity but failed to promote cytotoxic function in perforin knockout mice. Also, a markedly reduced therapy was noted in perforin knockout mice, implicating a role for CTL in Fab-SEA-mediated tumor eradication. The data suggest that Fab-SEA-targeted T cells may suppress tumor growth by both perforin-dependent cytotoxicity and local release of cytokines such as IFN-γ. The latter mechanism may have an important role in cytostatic effects against Ag-negative bystander tumor cells." @default.
• W4313343457 created "2023-01-06" @default.
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• W4313343457 date "1998-06-01" @default.
• W4313343457 modified "2023-10-14" @default.
• W4313343457 title "Perforin and IFN-γ Are Involved in the Antitumor Effects of Antibody-Targeted Superantigens" @default.
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• W4313343457 doi "https://doi.org/10.4049/jimmunol.160.11.5309" @default.
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