Abstract 3960: Whole body irradiation extends the duration of antitumor immunity toward established prostate tumors by adoptively transferred CD8+ T cells in TRAMP mice.

Abstract

Abstract Adoptive T cell transfer following whole body irradiation (WBI) can induce dramatic tumor regression in a subset of metastatic melanoma patients. We previously found that this approach also eliminates established autochthonous SV40 T-antigen induced murine brain tumors. However, the broader utility of this immunotherapy approach has not been systematically evaluated in solid tumors of different tissue origin. Here, we assessed the efficacy of applying WBI with adoptive T cell transfer to an SV40 T-antigen driven murine model of prostate cancer (TRAMP) previously shown to rapidly tolerize tumor-specific CD8+ T cells. TRAMP mice bearing established prostate tumors were treated with 475cGy WBI followed by adoptive transfer of T-antigen-specific T cell receptor transgenic CD8+ T cells. Accumulation, phenotype and function of the transferred T cells were monitored by flow cytometry, while therapeutic impact on mouse prostate tumors was assessed by histological scoring. Transferred T cells proliferated in both irradiated and non-irradiated TRAMP mice, but accumulated to significantly higher levels and persisted longer in the secondary lymphoid organs and prostate of irradiated mice. WBI also significantly increased the proportion of T cells that produced the effector molecule granzyme B. Prostate-infiltrating T cells in both treatment groups exhibited an effector differentiated phenotype, although neither developed a significant population of IFNγ-producing cells. Gross observations revealed that the urogenital tract in irradiated TRAMP mice was significantly smaller than that of non-irradiated mice two weeks after transfer, corresponding with a modest but statistically significant drop in pathological score. By three weeks after transfer, when prostate-infiltrating T cells had dramatically contracted in irradiated TRAMP mice, cumulative histological scores were generally equivalent although only mice in the non-irradiated treatment group had progressed to adenocarcinoma. Our results suggest that the addition of irradiation extends the persistence of functional tumor-specific T cells in the highly tolerogenic microenvironment of the TRAMP prostate. T cell accumulation was associated with a short-term delay in progression of established tumors. Citation Format: Lindsay Ward-Kavanagh, Timothy Cooper, Todd D. Schell. Whole body irradiation extends the duration of antitumor immunity toward established prostate tumors by adoptively transferred CD8+ T cells in TRAMP mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3960. doi:10.1158/1538-7445.AM2013-3960