Idiotypic cascades after injection of the monoclonal antibody OC125. A study in a mouse model.

In an animal model, we evaluated the possibility to induce antibodies directed against the tumor-associated antigen CA125 by immunization with the anti-CA125 antibody OC125 via activation of the idiotypic network. Our results show that Balb/c mice, immunized by repeated administrations of F(ab')2-fragments of the OC125 antibody (Ab1), produced anti-idiotypic antibodies (Ab2). The binding of these antibodies to the OC125 could be completely inhibited by the antigen CA125, suggesting that the anti-idiotypic antibodies imitate the original target antigen of the OC125. After induction of these paratope-binding anti-idiotypic antibodies (Ab2 beta), a murine IgG-anti-CA125 (Ab3) response arose in the same mice. The induction of idiotypic cascades offers the possibility of immunization against tumor-associated antigens without using the original antigen and breaking antitumor tolerance.