Data from Immunotherapy for Human Renal Cell Carcinoma by Adoptive Transfer of Autologous Transforming Growth Factor β–Insensitive CD8+ T Cells

Purpose: Transforming growth factor-β (TGF-β) is a potent immunosuppressor that has been associated with tumor evasion from the host immune surveillance and, thus, tumor progression. We tested a novel immunotherapy for human renal cell cancer (RCC) using a technique that involves the adoptive transfer of autologous tumor–reactive, TGF-β–insensitive CD8+ T cells into human RCC–challenged immunodeficient mice to identify its potent antitumor responses.Experimental Design: The present study was conducted using a one-to-one adoptive transfer strategy to treat tumor-bearing severe combined immunodeficient (SCID/beige) mouse. The SCID/beige mice were humanized with peripheral blood mononuclear cells from patients with RCC (Hu-PBMC-SCID) before adoptive transfer. Autologous CD8+ T cells were expanded ex vivo using autologous patient's dendritic cells pulsed with the tumor lysate and rendered TGF-β insensitive by dominant-negative TGF-β type II receptor. In addition, human RCC cell lines were generated using patients' tumor cells injected into SCID/beige mice.Results: Using flow cytometry analysis, we confirmed the expression of the tumor-reactive, TGF-β–insensitive CD8+ T cells were the effector CD8+ cells (CD27−CDRA+). Adoptive transfer of autologous TGF-β–insensitive CD8+ T cells into tumor-bearing Hu-PBMC-SCID mice induced robust tumor-specific CTL responses in vitro, were associated with tumor apoptosis, suppressed lung metastasis, and prolonged survival times in vivo.Conclusion: The one-to-one adoptive transfer strategy is an ideal in vivo murine model for studying the relationship between TGF-β and immunosurveillance in RCC in vivo. Furthermore, this technique may offer the promise of a novel therapeutic option for the treatment of human patients with RCC. Clin Cancer Res; 16(1); 164–73