Biologic effects of gamma interferon pre-treatment followed by monoclonal antibody 17-1A administration in patients with gastrointestinal carcinoma.
Twenty-seven patients with metastatic adenocarcinoma of the colon or pancreas were treated with 400mg of monoclonal antibody 17-1A. This antibody, which binds to a cell surface glycoprotein moiety preferentially expressed by adenocarcinomas of the rectum, colon, pancreas, and stomach, is postulated to induce antibody-dependent monocyte cytotoxicity (ADMC) as a mechanism of tumor lysis. Therapy was preceded by four days of gamma interferon infusions, with the intent of activating peripheral blood monocytes, enhancing monocyte Fc receptor expression and increasing the likelihood of tumor lysis as reflected by enhanced ADMC directed against a colon carcinoma cell line (SW1116) which expresses 17-1A's target antigen. In this Phase I study patients were treated daily at one of the following gamma interferon dose levels (X 10(6) U/M2/day): 0.001, 0.01, 0.1, 1.0, 10.0, 40.0, 60.0, 80.0. Addition of 100 U/ml of rIFN-gamma in vitro to monocytes isolated from normal controls or from patients prior to treatment significantly enhanced monocyte Fc receptor expression and ADMC. in vitro tumor cell killing by monocytes and monoclonal antibody was enhanced by treatment with low doses of rIFN-gamma, while treatment with high doses of rIFN-gamma did not enhance ADMC. No objective clinical responses were noted, although serum tumor markers dropped transiently in 36% of the treated patients. Seven of 11 assayed patients developed human anti-idiotype antibodies. With better scheduling of rIFN- and 17-1A we hope to duplicate optimal in vitro conditions for antibody-mediated cytotoxicity, hopefully enhancing in vivo antibody mediated tumor lysis.
D000230:Adenocarcinoma / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use* / Q000633:toxicity; D003602:Cytotoxicity, Immunologic; D004341:Drug Evaluation; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000627:therapeutic use*; D009000:Monocytes / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000628:therapy*; D011961:Receptors, Fc / Q000032:analysis
D000911:Antibodies, Monoclonal; D011961:Receptors, Fc; D007371:Interferon-gamma