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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.
Insights
Adoptive immunotherapy effectively regressed established tumors in mice using T-lymphocytes. This approach shows promise for treating weakly immunogenic cancers, but requires host immune suppression for success.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Methylcholanthrene-induced sarcomas (MCA 105 and MCA 106) in C57BL/6 mice exhibit weak immunogenicity.
- Tumor-associated transplantation antigens were poorly recognized, hindering natural immune rejection.
- Standard immunization methods with tumor cells and Corynebacterium parvum were only partially effective in inducing immunity.
Purpose of the Study:
- To investigate the efficacy of adoptive immunotherapy for established, weakly immunogenic tumors.
- To characterize new syngeneic mouse tumor models for immunotherapy research.
- To explore the mechanistic basis and requirements for successful adoptive immunotherapy.
Main Methods:
- Adoptive transfer of immune spleen cells into tumor-bearing mice.
- Immunization protocols involving tumor cells and Corynebacterium parvum.
- Assessment of tumor regression following cell transfer and host immune modulation.
Main Results:
- Adoptive transfer of sensitized spleen cells consistently induced complete regression of established MCA 105 and MCA 106 tumors.
- Therapy required prior immune suppression of the host, suggesting endogenous suppressive mechanisms.
- Irradiation of transferred T-lymphocytes abolished their therapeutic activity, confirming their role.
Conclusions:
- Adoptive immunotherapy is feasible and effective against established, weakly immunogenic tumors.
- Host immune suppression is critical for successful adoptive immunotherapy in these models.
- These tumor models offer valuable platforms for studying immunotherapy specificity and mechanisms.