Adoptive immunotherapy of newly induced murine sarcomas

S Shu, SA Rosenberg - Cancer research, 1985 - AACR
Cancer research, 1985AACR
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 106 tumor cells by tumor growth and excision. Specific immunity to reject a
106 tumor cell challenge could be elicited in less than 50% of mice by immunization with a …
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 106 tumor cells by tumor growth and excision. Specific immunity to reject a 106 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 108 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.
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