Monoclonal Antibodies in the Therapy of Minimally Residual Solid Tumors

Abstract

A review of the clinical trials on antibody-based cancer therapies reveals that this approach can, in rare cases, induce complete remissions in individual cancers. Since these trials have usually involved patients with large tumor masses, tumor cell inaccessibility is probably a major reason for the prevailing failures. Minimally residual disease, the stage when tumor cells are few and dispersed, should therefore be a more promising target for therapeutic antibodies. This hypothesis is supported by a prospective randomized trial on patients with resected Dukes C colorectal carcinoma. 189 patients were assigned to an observation regimen or to postoperative treatment with 500 mg of 17-1A antibody, followed by four 100-mg infusions each month. After a median follow-up of 5 years, antibody treatment reduced the overall death rate by 30% and decreased the recurrence rate by 27%. The effect of antibody was most pronounced in patients who had distant metastases as first sign of a relapse, an effect that was not seen for local relapses. Thus in addition to strategies designed to produce more effective, human-derived reagents, efforts need to be concentrated on directing passive antibody therapy towards the appropriate target.