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Immunogenicity of Human Melanoma-associated Antigens Defined by Murine Monoclonal Antibodies in Allogeneic and Xenogeneic Hosts¹

Department of Microbiology and Immunology, New York Medical College, Valhalla, New York 10595 [C. V. H., S. F.], and Departments of Pathology and Pediatrics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada [S-K. L., T. K.]

The immunogenicity in patients with melanoma, in monkeys, and in rabbits of four human melanoma-associated antigens (MAA) defined by murine monoclonal antibodies was investigated. The latter included the high molecular weight MAA and the (M_r 115,000, 100,000, and 95,000–150,000 MAA. To this end sera from patients with melanoma, from monkeys, and from rabbits immunized with cultured human melanoma cells were tested for their ability to inhibit the binding to cultured human melanoma cells of radiolabeled anti-M_r 95,000–150,000 MAA monoclonal antibody (MoAb) 140.72, anti-high molecular weight MAA MoAb 225.28, anti-M_r 115,000 MAA MoAb 345.134, and anti-M_r 100,000 MAA MoAb 376.96. None of the sera from patients with melanoma significantly inhibited the reactivity of any of the anti-MAA monoclonal antibodies with melanoma cells. Of the sera from the six monkeys immunized with human melanoma cells, two sera significantly inhibited the reactivity with cultured human melanoma cells of both MoAb 345.134 and 376.96, one serum inhibited only that of MoAb 345.134, and the remaining three sera did not inhibit any of the four anti-human MAA monoclonal antibodies. Sera from six of the seven rabbits immunized with cultured human melanoma cells inhibited the binding to melanoma cells of at least one of the four anti-human MAA monoclonal antibodies while the serum from one rabbit immunized with a melanoma cell extract had no effect. Marked differences were found among the individual rabbit sera in their ability to inhibit the binding of the four anti-human MAA monoclonal antibodies. Sequential immunoprecipitation experiments corroborated the serological findings obtained with one of the two rabbit antisera tested. These results suggest that the immunogenicity of human MAA in mice may be different from that in patients with melanoma and in other animal species.

¹ Supported by grants from the Medical Research Council of Canada (MA 5429) and from the J. P. Bickell Foundation, Toronto, Canada, and by USPHS Grant CA37959 awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed, at New York Medical College, Department of Microbiology & Immunology, Basic Sciences Building, Valhalla, New York, 10595.

Received 2/ 9/87. Revised 7/ 8/87. Accepted 7/ 9/87.

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