Immunotherapy for human renal cell carcinoma by adoptive transfer of autologous transforming growth factor β-insensitive CD8+ T cells

Longxin Wang, Weihong Wen, Jianlin Yuan, Brian Helfand, Yu Li, Changhong Shi, Feng Tian, Jia Zheng, Fuli Wang, Lin Chen, Lili Liang, Liqun Zhou, Chung Lee, Zhinan Chen, Yinglu Guo, He Wang, Qiang Zhang*, Weijun Qin

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)164-173
Number of pages10
JournalClinical Cancer Research
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wang, L., Wen, W., Yuan, J., Helfand, B., Li, Y., Shi, C., Tian, F., Zheng, J., Wang, F., Chen, L., Liang, L., Zhou, L., Lee, C., Chen, Z., Guo, Y., Wang, H., Zhang, Q., & Qin, W. (2010). Immunotherapy for human renal cell carcinoma by adoptive transfer of autologous transforming growth factor β-insensitive CD8+ T cells. Clinical Cancer Research, 16(1), 164-173. https://doi.org/10.1158/1078-0432.CCR-09-1758