- The 13762A rat mammary adenocarcinoma is a useful animal model for immunotherapy. Features of the tumor which correlate well with human breast cancer are its weak immunogenicity and propensity for metastasis. Rats cured of postsurgical, residual metastases by Corynebacterium parvum immunotherapy possessed strong, tumor-specific rejection immunity. A systemic adoptive transfer assay was employed to analyze components and regulation of tumor-rejection immunity in vivo.
Fewer oil-induced peritoneal exudate cells (PEC) than lymph node cells were required to transfer tumor-rejection immunity to naive recipients. Boosting of cured rat donors was necessary for optimal transfer of antitumor immunity. Recipients of immune lymphoid cells inhibited intradermal tumor growth and had a lower incidence of lung metastases. The adoptive immunity was specific since it strongly inhibited 13762A tumor growth but did not inhibit the growth of the antigenically unrelated R3230AC rat mammary tumor. PEC from rats sensitized to the bacterial immune stimulants used to effect cure were incapable of initiating tumor rejection in recipients. The same PEC, however, transferred delayed hypersensitivity to the appropriate bacterial antigens.
PEC were a mixed population of leukocytes consisting of macrophages, lymphocytes, and granulocytes. Macrophages or bone marrow-derived lymphocytes from immune donors did not transfer immunity. No immunity was conferred with serum from cured rats. Treatment of PEC with a xenogeneic antiserum specific for rat thymus-derived lymphocytes (T cells) abrogated transfer of tumor-rejection immunity. In addition, PEC contained lymphocytes reactive with monoclonal antibodies to differentiation antigens on rat T cells.
Cyclophosphamide (CY) treatment of recipients the day before transfer improved sensitivity of the assay. CY-pretreated, but not normal, recipients bearing established tumors allowed expression of tumor-rejection immunity. PEC from tumor-bearing rats were unable to transfer immunity unless donors were boosted with tumor cells. Under the conditions tested, spleen cells from tumor-bearers did not interfere with PEC-mediated transfer of tumor-rejection immunity. Likewise, serum from tumor-bearing or cured rats had no effect on 13762A growth, and was neither facilitative nor inhibitory to transfer of antitumor immunity with PEC.
Cured rats exhibited delayed hypersensitivity (DH) to 13762A tumor cells. Optimal responses were dose-related and dependent on recent exposure to tumor cells. The DH response was maximal 48 hours after challenge and was specific for 13762A tumor cells. Histological examination of DH reaction sites revealed the characteristic mononuclear cell infiltrate. Conditions appropriate for transfer of tumor-rejection immunity were inadequate for transfer of DH.
In summary, T cells from rats cured of 13762A tumor by immunotherapy were required for expression of tumor-rejection immunity in vivo.
- Dissertation Note:
- Ph.D. The Pennsylvania State University 1980.
- Source: Dissertation Abstracts International, Volume: 41-10, Section: B, page: 3733.
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