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Preparation of TGF-β insensitive cytotoxic T lymphocyte against prostate cancer and its antitumor activity
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Abstract:
Objective:To prepare TGFβ insensitive cytotoxic T lymphocytes（CTLs）against prostate cancer and to observe its therapeutic effect against prostate cancer. Methods: Peripheral blood mononuclear cells were obtained from prostate cancer patients, and were induced to differentiate into dendritic cells in vitro. Prostate cancer antigen was prepared from the same patients, and tumor antigen specific CTLs were induced by prostate tumor antigen impulsedDCs. The tumor antigen specific CTLs were infected with lentivirus containing TβRⅡDNglytk gene, and the response of TβRⅡDNglytk transfectedCTLs to TGFβ was examined by Western blotting analysis. Prostate cancer cellinoculated mice were treated with TGFβ sensitive and insensitiveCTLs separately, and the therapeutic results were compared. Results: CTLs induced by prostate tumor antigen impulsedDCs grew significantly faster than those induced by nonimpulsedDCs (P<001). TβRⅡDNglytk gene infection reduced the sensitivity of CTLs to TGFβ. The reaction of CTLs infected by lentiviral vector to TGFβ was significantly weaker than that of noninfected CTLs. TGFβ insensitive CTLs significantly inhibited the growth of implanted prostate tumors in mice. Conclusion: TGFβ insensitive prostate tumor antigen specific CTLs have apparent therapeutic effect against prostate cancer, which paves a way for immunotherapy of prostate cancer.
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Project Supported:
Supported by the Science and Technology Project of Tianjin（No. 07ZCGYSF01000）
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