Adoptive Transfer of Tumor-Reactive Transforming Growth Factor-β-Insensitive Cytolytic T Cells for Treatment of Established Mouse Renca Tumors

Objectives: To test, using a mouse renal cancer, Renca, whether adoptive transfer of tumor-reactive transforming growth factor (TGF)-β-insensitive cytolytic T cells can inhibit tumor progression. Methods: Cytolytic T cells were isolated from the spleen of male Balb/c mice repeatedly primed with irradiated Renca cells. They were expanded ex vivo and were rendered TGF-β-insensitive by infecting with a retrovirus containing dominant negative TGF-β type II receptor. Results: These tumor reactive TGF-β-insensitive cytolytic T cells showed a specific and robust tumor killing activity against Renca cells, but not irrelevant cells, using an in vitro cytotoxic assay. Adoptive transfer of cytolytic T cells was performed in mice 10 days after they were challenged with Renca cells (5 × 10⁵) by tail vein injection. At 30 days after the adoptive transfer, the pulmonary tumor counts in mice who had received TGF-β-insensitive cytolytic T cells (mean ± standard deviation 130 ± 140) was significantly less than those in mice that had received TGF-β-sensitive cytolytic T cells (305 ± 60) or in mice had received naive cytolytic T cells (375 ± 50; P < .01). Kaplan-Meier survival analysis indicated that mice that had received adoptive transfer of TGF-β-insensitive cytolytic T cells had a significantly greater rate of survival (75%) compared with mice that had received TGF-β-sensitive cytolytic T cells (35%) or naive cytolytic T cells (15%), respectively (P < .05). Conclusions: These results suggest that adoptive transfer of tumor-reactive TGF-β-insensitive cytolytic T cells can warrant consideration for renal cell cancer immunotherapy.