IMMUNOTHERAPY OF COLON-CANCER USING CHIMERIC MAB-31.1

We have produced two monoclonal antibodies specific for membranes of c olon carcinoma cells that demonstrate minimal if any cross reactivity with normal colon tissue. The antigen of one of the two antibodies (mA b 33.28) is extremely immunogenic eliciting both cell mediated and hum oral immunity. The monoclonal antibodies developed in in vitro studies suggested strong antibody dependent cell cytotoxicity (ADCC) for both antibodies, but somewhat stronger for the mAb 31.1. The murine versio n of mAb 31.1 produced approximately 90% tumor cell destruction in the same period of time. Nude mice with LS174T xenografts (human colon ca rcinoma) were challenged with 1 x 10(6) cells given subcutaneously in the thigh. By day 10, well animals were incapacitated by tumor growth. Among those animals receiving 400 mu g of intraperitoneal chimeric 31 .1 at day one, all were protected and remained free of disease. Those challenged with chimeric antibody and human effector cells at day 7 de monstrated regression of established tumor nodules among 80% of the an imals so treated. Therapy of patients with extensive primary as well a s metastatic colon cancer may be found to respond to the above form of therapy post surgery, when employed alone or in combination with an e ffective cytotoxic (chemotherapeutic) agent.