Immunotherapy of disseminated fibrosarcoma in mice using IL-2-producing tumor cells: Studies on its mechanism and specificity

Genetically modified, IL-2-producing tumor cells have been shown to regress in vivo and immunize mice against subsequent challenge with parental tumor . We investigated whether IL-2-producing tumor cells may serve as immunothe rapy of established tumors in mice. MCA 205 and MCA 203, weakly immunogenic murine sarcomas of B6 origin, were transfected with the pBMGNeo-mIL-2 vect or containing the murine IL-2 cDNA. Mice receiving intraperitoneal injectio ns of the parental sarcoma cells developed ascites and died within 4 weeks. The intraperitoneal injection of IL-2-producing tumor cells significantly prolonged survival and, moreover, significantly reduced the number of estab lished pulmonary metastases. The specificity of this effect was indicated b y the unaltered course of disease in mice that were injected with unrelated IL-2-producing tumor cells. FAGS analysis of peritoneal cells obtained fro m treated mice showed a predominance of V beta 3-positive cells. Tn a 4 h C r-51 release assay, these V beta 3-positive cells exhibited tumor-specific cytotoxicity and also nonspecific effector cells are shown to be involved i n tumor rejection.