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Abstract

One concept for immune therapy of patients bearing carcinomas involves monoclonal anti-idiotypic antibodies (Malds) to trigger the immune system of the host into a response against the tumor cells. Current theory states that so-called internal image Malds bearing epitopes specific to a given tumor associated antigen would be most suited for that purpose. We report here the generation of syngeneic Malds generated against the murine monoclonal immunoglobulin T84.66 (Abl), which defines a single epitope on the protein moiety of the carcinoembryonic antigen (CEA). This antigenic determinant is unique to CEA, as it is absent in other members of the CEA gene family that are expressed in a variety of normal human tissues, including granulocytes. The Mald 6G6.C4 (Ab2) exhibits the immunochemical features of an internal image antibody mimicking the epitope recognized by the idiotype T84.66. In enzyme immunoassays the binding of Abl to Ab2 is completely inhibited by CEA. In addition, Mald 6G6.C4 only binds to native but not to the denatured or reduced idiotype. Immunization of rabbits with F(ab′)2-fragments of 6G6.C4 results in antisera (Ab3) that show specificity to CEA in both binding and inhibition enzyme immunoassays as well as in Western blots. Finally, Ab3 did not detect NCA, a major CEA-related glycoprotein in Western blots, either in a purified form or in a crude tumor extract, indicating a high specificity of the anti-anti-idiotypic response. In summary, these immunochemical data show that the monoclonal anti-idiotype 6G6.C4 can functionally mimic a CEA specific epitope in rabbits and may do so in humans. Therefore, this antibody may have a clinical potential as a network antigen for active immune therapy in patients suffering from CEA positive carcinomas.