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Human High Molecular Weight-Melanoma Associated Antigen Mimicry by an Anti-Idiotypic Antibody: Characterization of the Immunogenicity and the Immune Response to the Mouse Monoclonal Antibody IMel-1¹

IDEC Pharmaceuticals Corp., La Jolla, California 92037 [P. C., S-V. K., S. R.]; Syntex, Palo Alto, California 94304 [N. B.]; Department of Microbiology, Montana State University, Bozeman, Montana 59717 [J. S.]; and Department of Microbiology and Immunology, New York Medical College, New York, New York 10595 [S. F.]

The mouse anti-idiotype (anti-id) monoclonal antibody (mAb) IMel-1 recognizes an idiotope in the antigen combining site of the immunizing anti-human high molecular weight melanoma-associated antigen (HMW-MAA) mAb 225.28. The mAb IMel-1 is able to induce an immune response against self cross-reacting HMW-MAA in rabbits that express HMW-MAA in normal tissues. Most of the rabbit anti-anti-id antibodies recognize a spatially distant determinant(s) from that defined by anti-HMW-MAA mAb 225.28. The immunogenicity of mAb IMel-1 is enhanced by its administration with the muramyl dipeptide-derived adjuvant. Anti-HMW-MAA antibodies were not detected in sera from rabbits immunized with HMW-MAA bearing cultured human melanoma cells. The differential immunogenicity of mAb IMel-1 and cell membrane bound HMW-MAA may account for the ability of anti-id mAb to induce anti-HMW-MAA immunity in patients who have not mounted such a response to HMW-MAA present in their lesions. Rabbit anti-HMW-MAA antibodies induced by anti-id mAb IMel-1 inhibited interactions of melanoma cells with elements of extracellular matrix. This may represent an additional mechanism by which anti-HMW-MAA immunity may affect the biology of melanoma cells in patients with melanoma immunized with anti-id mAb IMel-1.

¹ This work was supported by Small Business Innovation Research Grant CA 44246-02; by USPHS Grant CA 37959 awarded by the National Cancer Institute, Department of Health and Human Services; and by Grant IM500 awarded by the American Cancer Society.

² To whom requests for reprints should be addressed, at IDEC Pharmaceuticals Corp., 11099 North Torrey Pines Road, La Jolla, CA 92037.

Received 4/11/91. Accepted 9/ 3/91.

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