I期临床试验中，自体细胞因子诱导的杀伤细胞疗法对原发性肝细胞癌患者是安全的。
Autologous cytokine-induced killer cell therapy in clinical trial phase I is safe in patients with primary hepatocellular carcinoma.
作者信息
Shi Ming, Zhang Bing, Tang Zi-Rong, Lei Zhou-Yun, Wang Hui-Fen, Feng Yong-Yi, Fan Zhen-Ping, Xu Dong-Ping, Wang Fu-Sheng
机构信息
Research Center of Biotherapy, Beijing Institute of Infectious Diseases, 302 Hospital of PLA, Beijing 100039, China.
出版信息
World J Gastroenterol. 2004 Apr 15;10(8):1146-51. doi: 10.3748/wjg.v10.i8.1146.
AIM
To investigate the influence of autologous cytokine-induced killer (CIK) cells on the phenotypes of CIK effector cells, peripheral T lymphocyte subsets and dendritic cell subsets in patients with primary hepatocellular carcinoma (HCC).
METHODS
Peripheral blood mononuclear cells (PBMC) were collected by a blood cell separator from 13 patients with HCC, then expanded by priming them with interferon-gamma (IFN-gamma) followed by monoclonal antibody (mAb) against CD3 and interleukin-2 (IL-2) the next day. The phenotypic patterns of CIK cells were characterized by flow cytometry on d 0, 4, 7, 10, 13 and 15 of incubation, respectively. Then, 5 mL of venous blood was obtained from HCC patients before or 8-10 d after CIK cells were transfused into patients to assess the influence of CIK cells on the percentages of effector cells, and proportions of DC1 or DC2 in peripheral blood by flow cytometry.
RESULTS
After two weeks of in vitro incubation, the percentages of CD3(+)CD8(+), CD3(+)CD56(+), and CD25(+) cells increased significantly from 33.5+/-10.1%, 7.7+/-2.8%, and 12.3+/-4.5% to 36.6+/-9.0% (P<0.05), 18.9+/-6.9% (P<0.01), and 16.4+/-5.9% (P<0.05), respectively. However, the percentages of CD3(+)CD4(+) and NK cells had no significant difference. The percentages of CD3(+) and CD3(+)CD8(+) cells were kept at high levels during the whole incubation period, but those of CD25(+), and CD3(+)CD56(+) cells began to decrease on d 7 and 13, respectively. The proportions of type I dendritic cell (DC1) and type II dendritic cell (DC2) subsets increased from 0.59+/-0.23% and 0.26+/-0.12% before CIK cell therapy to 0.85+/-0.27% and 0.43+/-0.19% (all P<0.01) after CIK cell transfusion, respectively. The symptoms and characteristics of HCC patients were relieved without major side effects.
CONCLUSION
Our results indicated that autologous CIK cells can efficiently improve the immunological status in HCC patients, and may provide a potent approach for HCC patients as the adoptive immunotherapy.
目的
探讨自体细胞因子诱导的杀伤细胞（CIK）对原发性肝细胞癌（HCC）患者CIK效应细胞、外周血T淋巴细胞亚群及树突状细胞亚群表型的影响。
方法
采用血细胞分离机采集13例HCC患者的外周血单个核细胞（PBMC），先用γ干扰素（IFN-γ）刺激，次日再用抗CD3单克隆抗体（mAb）和白细胞介素-2（IL-2）进行扩增。分别在培养的第0、4、7、10、13和15天，通过流式细胞术对CIK细胞的表型进行分析。然后，在CIK细胞输注到患者体内之前或之后8 - 10天，采集HCC患者5 mL静脉血，通过流式细胞术评估CIK细胞对效应细胞百分比以及外周血中DC1或DC2比例的影响。
结果
体外培养两周后，CD3(+)CD8(+)、CD3(+)CD56(+)和CD25(+)细胞的百分比分别从33.5±10.1%、7.7±2.8%和12.3±4.5%显著增加至36.6±9.0%（P<0.05）、18.9±6.9%（P<0.01）和16.4±5.9%（P<0.05）。然而，CD3(+)CD4(+)和NK细胞的百分比无显著差异。在整个培养期间，CD3(+)和CD3(+)CD8(+)细胞的百分比保持在较高水平，但CD25(+)和CD3(+)CD56(+)细胞的百分比分别在第7天和第13天开始下降。I型树突状细胞（DC1）和II型树突状细胞（DC2）亚群的比例分别从CIK细胞治疗前的0.59±0.23%和0.26±0.12%增加至CIK细胞输注后的0.85±0.27%和0.43±0.19%（均P<0.01）。HCC患者的症状和体征得到缓解，且无严重副作用。
结论
我们的结果表明，自体CIK细胞可有效改善HCC患者的免疫状态，并可能为HCC患者提供一种有效的过继性免疫治疗方法。
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