Combination therapy for renal cell carcinoma using IFN-gamma and OK-432: in vitro study

Synergistic effect of recombinant IFN-gamma (IFN-gamma) and OK-432, a streptococcal preparation, using chromium release assay was studied in vitro on killer cell induction. The target cells utilized for assay were a human leukemia cell line K562, a human renal carcinoma cell line KU-2, autologous normal kidney tissues and autologous renal cell carcinomas. Culture supernatant of peripheral blood lymphocytes (PBL) and OK-432 (designated as OK conditioned medium or OK-CM) demonstrated enhanced cytotoxicity of fresh PBL against these target cells. Killer cell activity against autologous cancer cells could be also induced from PBL of renal cell carcinoma patients. Pretreatment of PBL with IFN-gamma revealed synergistic effect of OK-CM on killer cell induction. OK-CM derived from patients was shown to contain IL-2 activity as well as high titer of interferon. Neutralizing monoclonal antibody against IFN-gamma and IL-2 receptor demonstrated reduction of cytotoxicity. These results suggested potential benefit of sequential use of IFN-gamma and OK-432 for the treatment of metastatic renal cell carcinoma.