ADOPTIVE IMMUNOTHERAPY OF NEWLY INDUCED MURINE SARCOMAS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (4) , 1657-1662
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 5 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 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 [Propionibacterium acnes]. Adoptive transfer of spleen cells from property immunized mice consistency 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 a least 1 wk 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 this suppression could not be reconstituted by giving T-cell-depleted mice syngeneic spleen cells. The 2 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.