目的： 评价DC诱导的细胞毒性T淋巴细胞（cytotoxic T lymphocyte，CTL）治疗人乳头状瘤病毒（human papilloma virus，HPV）感染的8例宫颈癌（cervical cancer，CC）患者的临床疗效及安全性。 方法： 收集2010年11月至2012年5月在本院采用CTL细胞治疗HPV阳性的CC患者8例, 采集CC 患者外周血单个核细胞，以重组腺病毒介导HPV16/18 E6/E7转染DC细胞并诱导产生的CTL回输给患者，每次回输细胞量为1×10 9个，每2周回输一次，6次为一疗程。随访6～27个月，观察患者临床疗效和安全性。 结果： CTL细胞治疗的8例HPV感染的CC患者5例HPV转为阴性：其中治疗前缓解以及稳定状态的6例患者经CTL治疗后5例转为阴性，治疗前进展状态的2例患者无效；1例处于部分缓解状态的CC患者经CTL细胞治疗后达到完全缓解状态。全部治疗患者均无明显的不良反应。 结论： CTL细胞治疗HPV感染CC患者HPV感染转阴率高、可减缓病情进展且安全，更重要的是CTL细胞治疗为处于缓解以及稳定状态的HPV感染的CC患者提供了一条新的治疗途径。

Objective : To evaluate the efficacy and safety of dendritic cell (DC)-induced cytotoxic T lymphocytes (CTLs) in the treatment of patients with HPV-positive cervical cancer (CC). Method: Peripheral blood mononuclear cells (PBMCs) were collected from 8 HPV-infection CC patients who were admitted to our institute between November, 2010 and May, 2012. CTLs were generated by infecting the isolated PBMCs with adenoviral vector carrying HPV16/18 E6/E7 together with sequential stimulations with GM-CSF IL-4, TNF-α, IL-2 and IL-7 for once two weeks as an infusion. Patients were each treated with their own adenovirus-infected DC-CTLs through intravenous infusion twice a week for 3 weeks. Follow-up was performed for 6-27 months, during which patients’ response and adverse events were assessed. Result: Out of the 6 patients with partial remission/stable disease prior to treatment, 5 became HPV-negative. Adenovirus-infected DC-CTLs resulted in complete remission in 1 patient with partial remission prior to treatment but showed little effect in the 2 patients with a progressive disease prior to treatment. No significant adverse events were observed in any of the patients. Conclusion: Autologous transfusion of CTLs induced by DCs overexpressing HPV16/18 E6/E7 may offer a novel efficient and safe treatment for HPV-positive CC patients under a partial remission/stable disease state.

国家科技重大专项“十二五”计划基金资助项目（No. 2009zx09503）