Adoptive transfer of tumor-reactive transforming growth factor-beta-insensitive cytolytic T cells for treatment of established mouse Renca tumors

Urology
Weijun QinChung Lee

Abstract

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. 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. 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-b...Continue Reading

References

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Citations

Feb 11, 2014·Journal of the National Cancer Institute·Daniel R PrincipePaul J Grippo
Nov 18, 2009·Journal of Immunotoxicology·Ronan J Kelly, John C Morris
Apr 27, 2019·Frontiers in Oncology·Shabnum PatelConrad Russell Y Cruz

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