Induction of anti-idiotypic (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.