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. 1994 Sep 13;91(19):8945–8949. doi: 10.1073/pnas.91.19.8945

Monoclonal antibody-superantigen fusion proteins: tumor-specific agents for T-cell-based tumor therapy.

M Dohlsten 1, L Abrahmsén 1, P Björk 1, P A Lando 1, G Hedlund 1, G Forsberg 1, T Brodin 1, N R Gascoigne 1, C Förberg 1, P Lind 1, et al.
PMCID: PMC44723  PMID: 8090750

Abstract

The bacterial superantigen staphylococcal enterotoxin A (SEA) is an extremely potent activator of T lymphocytes when presented on major histocompatibility complex (MHC) class II molecules. To develop a tumor-specific superantigen for cancer therapy, we have made a recombinant fusion protein of SEA and the Fab region of the C215 monoclonal antibody specific for human colon carcinoma cells. SEA as part of a fusion protein showed a > 10-fold reduction in MHC class II binding compared to native SEA, and accordingly, the affinity of the FabC215-SEA fusion protein for the C215 tumor antigen was approximately 100-fold stronger than to MHC class II molecules. The FabC215-SEA fusion protein efficiently targeted T cells to lyse C215+ MHC class II- human colon carcinoma cells, which demonstrates functional substitution of the MHC class II-dependent presentation of SEA with tumor specificity. Treatment of mice carrying B16 melanoma cells expressing a transfected C215 antigen resulted in 85-99% inhibition of tumor growth and allowed long-term survival of animals. The therapeutic effect was dependent on antigen-specific targeting of the FabC215-SEA fusion protein, since native SEA and an antigen-irrelevant FabC242-SEA fusion protein did not influence tumor growth. The results suggest that Fab-SEA fusion proteins convey superantigenicity on tumor cells, which evokes T cells to suppress tumor growth.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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