T cell killing of human colon carcinomas by monoclonal-antibody-targeted superantigens.
The bacterial superantigen staphylococcal enterotoxin A (SEA) induces T cell activation as well as directing activated T cells to kill major-histocompatibility-complex-class-II-expressing tumours such as freshly prepared leukemia cells. We now report that conjugates of SEA and the colon-carcinoma-reactive mAb C215 mediate T-cell-dependent killing of freshly isolated cells obtained from surgical specimens of human colon carcinomas. Cytotoxicity was observed at nanomolar concentrations of conjugate while no or very low effects were seen with the mAb C215 or SEA alone. Tumour-infiltrating lymphocytes (TIL) did not exert any cytotoxicity against conjugate-treated tumour cells immediately after isolation. In vitro culture of TIL with interleukin-2 and SEA resulted in SEA-mAb-conjugate-dependent killing of freshly isolated tumour cells. This suggests that mAb-SEA conjugates may be of potential use to target T lymphocytes, including TIL, against colon carcinoma cells in vivo.
Lando
P A
PA
Kabi Pharmacia Therapeutics, Lund, Sweden.
Dohlsten
M
M
Hedlund
G
G
Akerblom
E
E
Kalland
T
T
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology; D002277:Carcinoma / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000008:administration & dosage*; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D066298:In Vitro Techniques; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; C026066:enterotoxin A, Staphylococcal