title: Adoptive transfer of tumor-reactive transforming growth factor-beta-insensitive cytolytic T cells for treatment of established mouse Renca tumors.
abstract: OBJECTIVE
  To test, using a mouse renal cancer, Renca, whether adoptive transfer of tumor-reactive transforming growth factor (TGF)-beta-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-beta-insensitive by infecting with a retrovirus containing dominant negative TGF-beta type II receptor.
  
  
  RESULTS
  These tumor reactive TGF-beta-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 x 10(5)) by tail vein injection. At 30 days after the adoptive transfer, the pulmonary tumor counts in mice who had received TGF-beta-insensitive cytolytic T cells (mean +/- standard deviation 130 +/- 140) was significantly less than those in mice that had received TGF-beta-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-beta-insensitive cytolytic T cells had a significantly greater rate of survival (75%) compared with mice that had received TGF-beta-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-beta-insensitive cytolytic T cells can warrant consideration for renal cell cancer immunotherapy.
authors: Department of Urology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shanxi Province, China.
authors: Weijun
authors: W
authors: Qin
authors: Feng
authors: F
authors: Tian
authors: Fuli
authors: F
authors: Wang
authors: Bin
authors: B
authors: Song
authors: He
authors: H
authors: Wang
authors: Qiang
authors: Q
authors: Zhang
authors: Borko
authors: B
authors: Jovanovic
authors: Lili
authors: L
authors: Liang
authors: Yinglu
authors: Y
authors: Guo
authors: Norm
authors: N
authors: Smith
authors: Chung
authors: C
authors: Lee
mesh_terms: D000818:Animals; D007680:Kidney Neoplasms / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000637:transplantation*; D016212:Transforming Growth Factor beta
chemical_list: D016212:Transforming Growth Factor beta