Reactivities of mouse monoclonal antibody K2.7 to renal cancers in complement dependent cytotoxicity and antibody dependent cell-mediated cytotoxicity.
Immunohistochemical analysis by indirect immunoperoxidase staining demonstrated that monoclonal antibody (mAb) K2.7, derived from a mouse immunized with a renal cell carcinoma (RCC) cell line OS-RC-2, reacted with 89 of 95 renal cancer tissues (94%). Only 1 gastric and uterine cancer tissue showed positive staining among 87 cancer specimens from 9 different organs. Among normal human tissues, the renal tubule, testis, epithelium of the uterine endometrial gland and Fallopian tube, grey matter of cerebrum and cerebellum, and foreskin showed positive staining. Serological analysis by protein A mixed hemadsorption (PA) assay demonstrated that mAb K2.7 reacted with 25 of 31 RCC cell lines (81%), but with only 2 of 50 other cell lines from different organs. The specific antitumor activities of mAb K2.7 against RCC cell lines were investigated in vitro by complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC) assays. In the CDC assay, all of the 9 RCC cell lines reactive serologically with mAb K2.7 were killed by mAb K2.7 with normal human serum, and the killing activity of mAb K2.7 correlated well with the reactivity of mAb K2.7 in the PA assay. mAb K2.7 showed the same killing activity against each of 3 RCC cell lines with sera from 9 patients with low and high stage renal cancers, as well as with normal human serum. In the ADCC assay, mAb K2.7 with peripheral blood leukocytes (PBLs) from 4 healthy donors showed cytotoxic activity against RCC cell lines. Peripheral blood leukocytes from the same 9 renal cancer patients also showed significant killing activity against the 3 RCC cell lines. These findings suggest the potential utility of mAb K2.7 for specific immunotherapy of renal cancer.
Kinouchi
T
T
Department of Urology, Center for Adult Diseases, Osaka, Japan.
Bander
N H
NH
Kotake
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D001921:Brain / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D002460:Cell Line; D002531:Cerebellum / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004717:Endometrium / Q000276:immunology; D005187:Fallopian Tubes / Q000276:immunology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000276:immunology*; D007684:Kidney Tubules / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D051381:Rats; D013205:Staphylococcal Protein A; D013274:Stomach Neoplasms / Q000276:immunology; D013737:Testis / Q000276:immunology; D014594:Uterine Neoplasms / Q000276:immunology
D000911:Antibodies, Monoclonal; D013205:Staphylococcal Protein A; D003165:Complement System Proteins