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Induction of Antigen-specific Immune Response with Use of Anti-Idiotypic Monoclonal Antibodies to Anti-Carcinoembryonic Antigen Antibodies¹

Department of Internal Medicine (Section 1), Sapporo Medical College, S-1, W-16, Chuo-ku, Sapporo, 060 [M. T., K. I., S. T., T. I., Y. H., A. Y.], Life Sciences Laboratories, Ajinomoto Co., Yokohama [Y. H.], Department of Basic Research, Hoechst Japan Limited, Kawagoe, Saitama [H. K.], Japan

Anti-idiotypic monoclonal antibodies (MoAbs) were prepared in a syngeneic system against anti-carcinoembryonic antigen (CEA) MoAb 5B3 (IgG1), which reacted with a carbohydrate moiety on CEA, and MoAb MA208 (IgG1), which reacted with a peptide on CEA. Antiidiotypic MoAb T3-503 and T4-202 recognized the private idiotype of MoAb 5B3; anti-idiotypic MoAb M7-049 and M7-625 did so for MoAb MA208. Idiotype mapping showed that MoAb 5B3 has at least two distinct idiotopes at its combining site and MoAb MA208 also has two. Four different anti-idiotypic MoAbs (Ab2) could induce anti-anti-idiotypic antibodies (Ab3) specific to their respective immunizing antiidiotypic MoAbs. Anti-anti-idiotypic MoAb M7-625 antiserum (at least a part of the antibodies) have the same reactivity as MoAb MA208, since the serum competed with the binding of MoAb MA208 against CEA and contained the antibody population reactive with purified CEA in immunoblotting assay. These results suggest that anti-idiotypic MoAb M7-625 bears the internal image of the antigen (CEA) and induces the anti-anti-idiotypic antibodies specific to CEA. Therefore, an anti-idiotypic antibody bearing the internal image of a tumor associated antigen might be used as a possible tool for vaccination or immunotherapy against malignant tumors as an antigen specific immunomodulator.

¹ Supported by grants for Cancer Research from the Ministry of Education, Science and Culture to A. Yachi and K. Imai, and from the Ministry of Health and Welfare, Japan, to A. Y. This work was also supported and encouraged by the Incitement Award of the Japanese Cancer Association to K. I.

² To whom requests for reprints should be addressed, at Department of Internal Medicine (Section 1), Sapporo Medical College, S-1, W-16, Chuo-ku, Sapporo 060 Japan.

Received 5/21/90. Accepted 3/ 7/91.