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 dem onstrated that monoclonal antibody (mAb) K2.7, derived from a mouse im munized with a renal cell carcinoma (RCC) cell Line OS-RC-2, reacted w ith 89 of 95 renal cancer tissues (94%). Only 1 gastric and uterine ca ncer 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 staini ng. Serological analysis by protein A mixed hemadsorption (PA) assay d emonstrated 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 spec ific antitumor activities of mAb K2.7 against RCC cell lines were inve stigated in vitro by complement dependent cytotoxicity (CDC) and antib ody dependent cell-mediated cytotoxicity (ADCC) assays. In the CDC ass ay, all of the 9 RCC cell lines reactive serologically with mAb K2.7 w ere killed by mAb K2.7 with normal human serum, and the killing activi ty 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 K 2.7 with peripheral blood leukocytes (PBLs) from 4 healthy donors show ed cytotoxic activity against RCC cell lines. Peripheral blood leukocy tes from the same 9 renal cancer patients also showed significant kill ing activity against the 3 RCC cell lines. These findings suggest the potential utility of mAb K2.7 for specific immunotherapy of renal canc er.