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Monoclonal Antibodies to Human Renal Cell Carcinoma: Recognition of Shared and Restricted Tissue Antigens¹

Departments of Urologic Surgery [R. L. V., T. D. M., R-K. C., J. A. N., D. F. P., P. H. L.] and Microbiology [R. L. V.], University of Minnesota Medical Center, Minneapolis, Minnesota 55455, and Veterans Administration Medical Center, Minneapolis, Minnesota 55417 [R. L. V., T. D. M., E. W. A., G. A. P., P. H. L.]

Monoclonal antibodies (MABs) reactive with human renal cell carcinoma (RCC) were generated following immunization of mice with either RCC homogenates, RCC cell lines, or fetal kidney homogenates. The characteristics of four highly reactive immunoglobulin G1 MABs, designated UMVA-RCC-A6H, UMVA-RCC-A36, UMVA-RCC-C5H and UMVA-RCC-D5D are presented. The screening process consisted of a cell binding enzyme-linked immunosorbent assay and immunohistological examination of tumor, normal, and fetal tissue sections. The MABs illustrated various degrees of antigen restriction: A6H identified an antigen common to RCC, some lung and colon carcinomas, the proximal renal tubules but no other normal tissues; A36 reacted with most human tumors, the renal tubules, and many other normal tissues; C5H reacted with nearly every human cancer but of the normal tissues, only the renal glomerulus shared this antigen; D5D was very restrictive, reacting with many although not all RCC and no other cancers or normal tissues with the exception of an occasional reactivity with a Bowman's capsule. Metastatic RCC and RCC xenografts expressed these antigens. None of the MABs participated in complement-mediated cytotoxicity. In immunoprecipitation studies with L-[methyl-³H]methionine and [³H]glucosamine-HCl metabolically labeled RCC cells, C5H was shown to be associated with an antigen of M_r 115,000.

¹ Supported in part by Veterans Administration Medical Research funds and a Clinical Fellowship, American Cancer Society Grant 05417.

² To whom requests for reprints should be addressed, at Veterans Administration Medical Center, 54th Street and 48th Avenue S., Minneapolis, MN 55417.

Received 1/14/85. Revised 8/16/85. Accepted 8/21/85.