Abstract
In our institution, over 200 patients with gastro-intestinal tract carcinomas have been treated with monoclonal antibodies (MAbs) including CO 17-1A. In one clinical trial, MAbs were administered in combination with gamma interferon. Natural killer cell cytotoxicity (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC) were studied in patients before treatment. Very low NK and ADCC activities were measured in metastatic cancer patients. NK cell lysis was enhanced during γ-interferon treatment, associated with a modification of the Fc receptor expression, but no changes in the ADCC reactivities of leukocytes were noticed. Monoclonal antibodies were circulating for one to four weeks after a single dose infusion, independent of the patients' immune responses toward the administered MAb. Sixty-three percent of the patients mounted an anti-mouse immunoglobulin response. Anti-idiotypic antibodies were detected in 70% of the responding patients. Variations in the anti-mouse Ig responses were dependent on the therapeutic protocol. The immune responses were composed of IgM, IgA, and IgG (mainly IgG1, often associated with IgG2 and/or IgG3). In patients receiving MAbs together with γ-interferon, development of the anti-mouse Ig responses were delayed with an increase in the anti-isotypic component and a decrease in the anti-idiotypic component as compared to patients treated with MAb alone. No correlation could be established with clinical results.
Get full access to this article
View all access options for this article.