MONOCLONAL-ANTIBODIES TO HUMAN RENAL-CELL CARCINOMA - RECOGNITION OF SHARED AND RESTRICTED TISSUE ANTIGENS

Abstract

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 issues, 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 CC xenografts expressed these antigens. None of the MABs participated in complement-mediated cytotoxicity. In immunoprepitation studies with L-[methyl-3H]methionine and [3H]glucosaline-HCl metabolically labeled RCC cells, C5H was shown to be associated with an antigen of Mr 115,000.