INDUCTION OF ANTIIDIOTYPIC (AB2) AND ANTI-ANTI-IDIOTYPIC (AB3) ANTIBODIES IN PATIENTS TREATED WITH THE MOUSE MONOCLONAL-ANTIBODY 17-1A (AB1) - RELATION TO THE CLINICAL OUTCOME - AN IMPORTANT ANTITUMORAL EFFECTOR FUNCTION

Forty-three patients with metastatic colorectal carcinoma (CRC) were treated with the unconjugated mouse monoclonal antibody (MAb) 17-1A (ab1) only. The presence of antiidiotypic antibodies (ab2) and anti-antiidiotypic antibodies (ab3) were analyzed using an ELISA technique and a mixed hemadsorption assay respectively. Ninety-five percent (41/43) of the patients developed ab2 both of the IgM and the IgG classes. Forty-seven percent (20/43) of the patients had detectable ab3 after therapy, two of them also before administration of MAb 17-1A. Binding in vitro of ab3 (ab1') to CRC cells could be specifically inhibited by ab1. Ab3 bound to human monoclonal antiidiotypic antibodies and to a goat antiidiotypic antibody (ab2). Both these ab2 were directed against MAb 17-1A (ab1). There was a strong correlation between the presence of ab3 and the clinical outcome. Ab3+ patients survived significantly longer than those who did not develop ab3 antibodies, 80 weeks vs 38 weeks (p < 0.001). A statistically significant correlation was found between the presence of ab3 and the anti-tumor response (CR+PR+MR+SD) (p = 0.01). Thus, induction of an antiidiotypic cascade seems to be an important antitumor effector function of MAb in the treatment of cancer patients.