Wang Fu-Sheng, Liu Ming-Xu, Zhang Bing, Shi Ming, Lei Zhou-Yun, Sun Wen-Bing, Du Qing-You, Chen Ju-Mei
Division of Biological Engineering, Beijing Institute of Infectious Diseases, 26 Fengtai Road, Beijing 100039, China.
World J Gastroenterol. 2002 Jun;8(3):464-8. doi: 10.3748/wjg.v8.i3.464.
To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptive immunotherapy for the patients with primary hepatocellular carcinoma (HCC), we evaluated the proliferation rate, phenotype and the antitumor activity of human CIK cells from healthy donors and HCC patients in vitro and in vivo.
Peripheral blood mononuclear cells (PBMC) from healthy donors and patients with primary HCC were incubated in vitro and induced into CIK cells in the presence of various cytokines such as interferon-gamma (IFN-gamma), interleukin-1 (IL-1), IL-2 and monoclonal antibody (mAb) against CD3. The phenotype and characterization of CIK cells were identified by flow cytometric analysis. The cytotoxicity of CIK cells was determined by (51)Cr release assay.
The CIK cells were shown to be a heterogeneous population with different cellular phenotypes. The percentage of CD3+/CD56+ positive cells, the dominant effector cells, in total CIK cells from healthy donors and HCC patients, significantly increased from 0.1-0.13% at day 0 to 19.0-20.5% at day 21 incubation, which suggested that the CD3+ CD56+ positive cells proliferated faster than other cell populations of CIK cells in the protocol used in this study. After 28 day in vitro incubation, the CIK cells from patients with HCC and healthy donors increased by more than 300-fold and 500-fold in proliferation cell number, respectively. CIK cells originated from HCC patients possessed a higher in vitro antitumor cytotoxic activity on autologous HCC cells than the autologous lymphokine-activated killer (LAK) cells and PBMC cells. In in vivo animal experiment, CIK cells had stronger effects on the inhibition of tumor growth in Balb/c nude mice bearing BEL-7402-producing tumor than LAK cells (mean inhibitory rate, 84.7% vs 52.8%, P<0.05) or PBMC (mean inhibitory rate, 84.7% vs 37.1%, P<0.01).
Autologous CIK cells are of highly efficient cytotoxic effector cells against primary hepatocellular carcinoma cells and might serve as an alternative adoptive therapeutic strategy for HCC patients.
为了表征细胞因子诱导的杀伤细胞（CIK）的抗癌功能，并为原发性肝细胞癌（HCC）患者开发过继性免疫疗法，我们在体外和体内评估了来自健康供体和HCC患者的人CIK细胞的增殖率、表型和抗肿瘤活性。
将来自健康供体和原发性HCC患者的外周血单个核细胞（PBMC）在体外培养，并在各种细胞因子如干扰素-γ（IFN-γ）、白细胞介素-1（IL-1）、IL-2和抗CD3单克隆抗体（mAb）存在的情况下诱导成为CIK细胞。通过流式细胞术分析鉴定CIK细胞的表型和特征。通过（51）Cr释放试验测定CIK细胞的细胞毒性。
CIK细胞显示为具有不同细胞表型的异质群体。在健康供体和HCC患者的总CIK细胞中，占主导地位的效应细胞CD3 + / CD56 +阳性细胞的百分比在培养第0天的0.1 - 0.13%显著增加至培养第21天的19.0 - 20.5%，这表明在本研究使用的方案中，CD3 + CD56 +阳性细胞比CIK细胞的其他细胞群体增殖更快。体外培养28天后，来自HCC患者和健康供体的CIK细胞在增殖细胞数量上分别增加了300倍和500倍以上。源自HCC患者的CIK细胞对自体HCC细胞的体外抗肿瘤细胞毒性活性高于自体淋巴因子激活的杀伤（LAK）细胞和PBMC细胞。在体内动物实验中，CIK细胞对携带产生BEL-7402肿瘤的Balb/c裸鼠的肿瘤生长抑制作用比LAK细胞（平均抑制率，84.7%对52.8%，P<0.05）或PBMC（平均抑制率，84.7%对37.1%，P<0.01）更强。
自体CIK细胞是针对原发性肝细胞癌细胞的高效细胞毒性效应细胞，可能作为HCC患者的一种替代性过继性治疗策略。
