HLA半相合NK细胞过继治疗肝癌的一期临床试验

肝脏 ›› 2017, Vol. 22 ›› Issue (7): 581-584.

HLA半相合NK细胞过继治疗肝癌的一期临床试验

谢云波,张纪元,杨涛,金磊,王松山,廉方,曲芮,马晓芬,施明,段海峰,王福生

100850 北京军事医学科学院放射与辐射医学研究所(谢云波,段海峰);解放军第三○二医院感染性疾病研究与诊疗中心(谢云波,张纪元,杨涛,金磊,王松山,廉方,曲芮,马晓芬,施明,王福生)

收稿日期:2017-01-27 出版日期:2017-06-15 发布日期:2020-06-16
通讯作者: 段海峰,Email: duanhf0720@163.com;王福生,Email: fswang302@163.com

Phase Ⅰ study of HLA-halfmatched allogeneic natural killer cells therapy in patients with hepatocellular carcinoma

XIE Yun-bo, ZHANG Ji-yuan, YANG Tao, JIN Lei, WANG Song-shan, LIAN Fang, QU Rui, MA Xiao-fen, SHI Ming, DUAN Hai-feng, WANG Fu-sheng.

Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China; Research and Treatment Center of Infectious Diseases, Beijing 302 Hospital, Beijing 100039, China

Received:2017-01-27 Online:2017-06-15 Published:2020-06-16
Contact: DUAN Hai-feng,Email: duanhf0720@163.com;WANG Fu-sheng,Email: fswang302@163.com

摘要/Abstract

摘要： 目的了解肝癌患者过继回输异体自然杀伤(natural killer, NK)细胞后的安全性。方法选择4例经手术或放化疗后的肝癌患者,回输其直系亲属来源体外培养的NK细胞。观察记录培养过程中NK细胞数量、表型及杀伤功能。观察肝癌患者异体NK细胞过继回输反应,检测并记录基线及治疗后4、12周患者肝肾功能、血常规、凝血及肿瘤标志物。结果供者外周血单个核细胞扩增培养可得到2×10⁹~5×10⁹个细胞,其中NK细胞占总细胞数的49%~83%。体外杀伤实验表明,培养的NK细胞对HepG2肝癌细胞系具有显著的杀伤能力,并与效靶比呈正相关,添加IL-2可以进一步提高NK细胞对HepG2细胞的杀伤能力。回输后,4例肝癌患者无GVHD反应,肝功能、肾功能、心血管功能正常。2例患者有一过性体温升高,其中1例最高为38.5℃,持续4 h,另1例最高为37.8℃,持续7 h,未经任何治疗均自行缓解。结论直系亲属来源的HLA半相合NK细胞过继治疗具有良好的安全性。

关键词: 肝癌, 细胞治疗, NK细胞

Abstract: Objective To investigate the safety of allogeneic natural killer (NK) cells transfusion in patients with hepatocellular carcinoma (HCC).Methods Four patients with HCC after operation or chemotherapy were enrolled in this study, and received transfusion of NK cells derived from their immediate family. Numeric, phenotypic and functional characteristics of the NK cells cultured in vitro were observed. Moreover, liver function, kidney function, coagulation time test, blood routine and serum tumor markers of patients were measured at baseline and at week 4 and 12 after the transfusion, respectively.Results About 2~5×10⁹ mononuclear cells were collected from 50~80 mL peripheral blood of donors, in which NK cells accounted for 49%~83%. The cytolytic assay showed that cultured NK cells could kill HepG2 cells in a dose-dependent manner, and the cytotoxicity of NK cells were further enhanced by interleukin-2. After transfusion, no patients showed occurrence of graft-vs-host disease (GVHD) or significant changes in liver, kidney and heart functions. Two patients had transient body temperature rising and relieved by themselves.Conclusion Histocompatibility antigens (HLA) half matched allogeneic NK cell transfusion therapy in HCC patients is safe and tolerable.

Key words: Hepatocellular carcinoma, Cell therapy, Natural killer cells

谢云波,张纪元,杨涛,金磊,王松山,廉方,曲芮,马晓芬,施明,段海峰,王福生. HLA半相合NK细胞过继治疗肝癌的一期临床试验[J]. 肝脏, 2017, 22(7): 581-584.

XIE Yun-bo, ZHANG Ji-yuan, YANG Tao, JIN Lei, WANG Song-shan, LIAN Fang, QU Rui, MA Xiao-fen, SHI Ming, DUAN Hai-feng, WANG Fu-sheng.. Phase Ⅰ study of HLA-halfmatched allogeneic natural killer cells therapy in patients with hepatocellular carcinoma[J]. Chinese Hepatolgy, 2017, 22(7): 581-584.

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