Tumor-reactive superantigens suppress tumor growth in humanized SCID mice.

Superantigens are extremely potent activators of T lymphocytes. To develop a tumor-reactive superantigen for cancer therapy, we made a recombinant fusion protein of the superantigen staphylococcal enterotoxin A (SEA) and the Fab region of the C242 monoclonal antibody (C242Fab-SEA), which recognize human colon carcinoma cells. The therapeutic effect of C242Fab-SEA on colon-cancer growth was examined in lymphocyte-engrafted humanized SCID mice bearing intraperitoneally growing Colo205 colon carcinomas. i.v. injections of C242Fab-SEA significantly inhibited tumor growth. The anti-tumor effect required the presence of human T cells in the SCID mice. Optimal therapeutic effects were seen with C242Fab-SEA, but not with C242Fab fragment or SEA alone, demonstrating that both entities of the fusion protein were required. C242Fab-SEA-treated tumors showed a massive infiltration of T cells in the tumor parenchyme, and was accompanied by enhanced expression of ICAM-I and HLA-DR on the tumor cells. The results demonstrate that Fab-SEA fusion proteins convey superantigenicity on tumor cells which evoke T-cell-dependent suppression of tumor growth.