Detection of Human Antibodies Generated Against Therapeutic Antibodies Used in Tumor Therapy

Application of monoclonal antibodies (MAb) for therapeutic purpose may induce the formation of human antibodies directed against the immunogenic epitopes, which are presented on the therapeutic MAb. Formation of such human antibodies mostly is an undesired side effect, but in the case of newly developed immunotherapeutic tumor treatment strategies it represents the underlying therapeutic effect. Especially the formation of so-called “internal image” antibodies, which are directed against the antigen-combining site (paratope) of the therapeutic antibody, is supposed to evoke specific immune responses against tumor antigens mediated via idiotype-anti-idiotype interactions within the immunoregulatory network. For the monitoring of the immune response after antibody application, the newly formed human antibodies can be measured with immunoassay procedures involving the applied therapeutic antibody as test antibody. Because the original antigen is directed against the therapeutic antibody and inhibits the binding of “internal image” antibodies, a special assay design is needed to avoid interferences with samples containing the antigen. We describe an immunoassay procedure that allows the correct quantification of antiidiotypic antibodies including “internal image” antibodies that are not affected by the original antigen or other serum components that may interact with the therapeutic antibody.