Adoptive transfer of tumor-reactive transforming growth factor-beta-insensitive cytolytic T cells for treatment of established mouse Renca tumors.
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.
Qin
Weijun
W
Department of Urology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shanxi Province, China.
Tian
Feng
F
Wang
Fuli
F
Song
Bin
B
Wang
He
H
Zhang
Qiang
Q
Jovanovic
Borko
B
Liang
Lili
L
Guo
Yinglu
Y
Smith
Norm
N
Lee
Chung
C
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
D016212:Transforming Growth Factor beta