目的：制备TGFβ不敏感前列腺癌特异性CTLs，观察其对前列腺癌的治疗作用。方法：分离前列腺癌患者外周血单个核细胞，体外诱导DCs；制备该患者前列腺癌肿瘤抗原，冲击DCs后诱导肿瘤特异性CTLs；用携带TβRⅡDNglytk基因的慢病毒感染肿瘤特异性CTLs；Western blotting检测TβRⅡDNglytk感染后CTLs对TGFβ的敏感性。分别以TGFβ敏感和不敏感CTLs治疗小鼠前列腺癌移植瘤，比较其疗效。结果：前列腺癌组织抗原冲击后DCs诱导的肿瘤特异性CTLs生长速度快于未冲击DCs组（P<0.01），其活化状态标志CD25的表达显著高于对照CTLs(P<0.01)。TβRⅡDNglytk慢病毒感染使肿瘤特异性CTLs对TGFβ敏感性减弱。TGFβ不敏感的CTLs可显著抑制荷瘤鼠前列腺癌的生长(P<0.01)。结论：成功制备的TGFβ不敏感前列腺癌特异性CTLs对小鼠前列腺移植瘤有明显的治疗作用，为前列腺癌免疫治疗奠定了一定的实验基础。

Objective:To prepare TGFβ 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 impulsedDCs. The tumor antigen specific CTLs were infected with lentivirus containing TβRⅡDNglytk gene, and the response of TβRⅡDNglytk transfectedCTLs to TGFβ was examined by Western blotting analysis. Prostate cancer cellinoculated mice were treated with TGFβ sensitive and insensitiveCTLs separately, and the therapeutic results were compared. Results: CTLs induced by prostate tumor antigen impulsedDCs grew significantly faster than those induced by nonimpulsedDCs (P<001). TβRⅡDNglytk gene infection reduced the sensitivity of CTLs to TGFβ. The reaction of CTLs infected by lentiviral vector to TGFβ was significantly weaker than that of noninfected CTLs. TGFβ insensitive CTLs significantly inhibited the growth of implanted prostate tumors in mice. Conclusion: TGFβ insensitive prostate tumor antigen specific CTLs have apparent therapeutic effect against prostate cancer, which paves a way for immunotherapy of prostate cancer.

天津市科技计划资助项目（No. 07ZCGYSF01000）