Monoclonal Antibody in Cancer Therapy

Sears, Henry

Abstract

We have completed two immunotherapy trials using a IgG2a isotype murine monoclonal antibody - 1083-17-1A - in patients with adenocarcinoma of the gastrointestinal tract. More than 40 patients with advanced gastrointestinal cancer have had doses of 15-1000 mg of antibody injected intravenously into the hepatic artery without any evidence of toxicity. Anti-murine antibodies have been detected in 70% of those patients infused with 150 mg or less of antibody, whereas only 2 of 13 patients developed such a response when the administered dose exceeded 250 mg. Seven patients, who have not had circulatory anti-murine antibodies, have received repeated 100-350 mg without any evidence of adverse reaction. Sustained remissions have been observed in 4 patients, which another 4 have been potentially cured of their recurrent or metastatic rectal or pancreatic adenocarcinomas. All but one of these patients were in the earlier smaller dosage part of the trial, and had a greater likelihood of being immunized.
The aim of this proposal (a continuation) is to evaluate the immunotherapeutic potential of 17-1A IgG2a antibody in a more selected population of patients, whose gastrointestinal tumors can be destroyed or their growth retarded. We will determine if previous treatment regimens, tumor size or burdens or the patient's immune status effect the anti-tumor action of 17-1A antibody. The determination of exact dosage of murine immunoglobulin evoking or abolishing immune response, and the number and dosage of immunoglobulin injections necessary to maintain antibody circulation will be sought. In all patients the humoral, including anti-idiotypic response, and cellular immune responses will be studied to evaluate the relationship between the patient's immune response to the murine immunoglobulin and the immunotherapeutic effect on the tumor.