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.
Lando
P A
PA
Department of Tumor Immunology, Wallenberg Laboratory, University of Lund, Sweden.
Dohlsten
M
M
Ohlsson
L
L
Kalland
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D004768:Enterotoxins / Q000627:therapeutic use*; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D018089:Superantigens / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D006684:HLA-DR Antigens; D007140:Immunoglobulin Fab Fragments; D011993:Recombinant Fusion Proteins; D018089:Superantigens; D018799:Intercellular Adhesion Molecule-1; C026066:enterotoxin A, Staphylococcal