Antitumor activity of murine monoclonal antibody NCC-ST-421 on human cancer cells by inducing apoptosis.

BACKGROUND: The murine monoclonal antibody NCC-ST-421 (ST-421) recognizes dimeric Le(a) antigen expressed on gastrointestinal cancer cells. MATERIALS AND METHODS: Direct antitumour activity of ST-421 was evaluated using dimeric Le(a) positive cell lines Colo 205, Colo 201, HT-29 and WiDr; and negative cell lines MX-1 and K562. RESULTS: While time- and concentration-dependent antitumour activity was observed against Colo 205 and Colo 201, no antitumour activity was detected against the other cell lines tested in an in vitro cytotoxicity assay. When ST-421 was administered intraperitoneally daily for 2 weeks to severe combined immunodeficient (SCID) mice transplanted with tumour xenografts, inhibition of tumour growth was observed against Colo 205, and to a lesser extent HT-29 and WiDr. Anti-asialo GM1 antibody did not block this antitumour activity, suggesting ST-421 has a direct cytotoxic effect. The degree of antitumour activity of ST-421 dependent on the grade of Le(a)-expression as detected by immunohistochemical staining. CONCLUSIONS: Flow cytometric and immunohistochemical analysis suggests the induction of apoptosis may play a key role in the direct antitumour activity of ST-421 on Colo 205 cells.