Adoptive immunotherapy of newly induced murine sarcomas

Abstract

Two newly induced methylcholanthrene sarcomas of C57BL/6 mouse origin were selected for studies of the adoptive immunotherapy of established tumors. The MCA 105 and MCA 106 tumors, used during their first five transplant generations, possessed weakly immunogenic tumor-associated transplantation antigens as revealed by failure to elicit immunity to reject 10(6) tumor cells by tumor growth and excision. Specific immunity to reject a 10(6) tumor cell challenge could be elicited in less than 50% of mice by immunization with a mixture of viable tumor cells and Corynebacterium parvum. Adoptive transfer of spleen cells from properly immunized mice consistently mediated the regression of established MCA 105 and MCA 106 tumors. Following systemic administration of 10(8) immune cells into mice bearing palpable tumor, the tumor grew for at least 1 week and then completely regressed. The adoptive immunotherapy was immunologically specific for each of these tumors and was mediated by sensitized T-lymphocytes. Irradiation (1000 R) of the transferred cells abrogated their in vivo activity. With both tumors, successful therapy required prior immune suppression of the host. This latter finding suggested the existence of suppression mechanisms mediated by tumor-bearing mice although we have been unable to reconstitute this suppression by giving T-cell-depleted mice syngeneic spleen cells. The two new animal tumor models characterized in this study not only demonstrate the feasibility of adoptive immunotherapy to weakly immunogenic tumors but also provide unique opportunities for mechanistic studies of the specificity of adoptive immunotherapy.