CLOSTRIDIUM-DIFFICILE TOXIN-A THERAPY FOR HCT-116 HUMAN COLON-CANCER IN NUDE-MICE

Clostridium difficile toxin A was evaluated for an antitumor effect in vivo on HCT 116 human colon carcinoma cells growing subcutaneously in nude mice. A mean reduction in tumor volume of at least 65%, by measu rement in three dimensions, was observed in mice who received two 9- t o 13-day courses of daily intraperitoneal injections of toxin A as com pared to mice receiving diluent alone. Reversible adverse effects of t oxin A were noted in some animals, consisting primarily of liver toxic ity and skin rash. HCT 116 cells in toxin A-treated mice grew as flatt ened tumors with ulcerated centers compared to rounded tumors without ulceration in controls. Histologic examination of tumors from represen tative mice revealed that two thirds of the tumor in a treated mouse w as necrotic compared to only one third in a control, suggesting greate r antitumor efficacy of toxin A than estimated by tumor measurements a lone. (C) 1994 Wiley-Liss, Inc.