CIK细胞及其在肿瘤治疗中的应用

doi:10.3760/cma.j.issn.1673-422X.2015.02.013

摘要/Abstract

摘要： 细胞因子诱导的杀伤（CIK）细胞过继免疫治疗在实体肿瘤治疗中发挥重要作用，特别是对于经标准治疗后出现复发或转移的实体肿瘤来说具有广阔的应用前景。尽管许多过继免疫治疗策略已经在临床前研究中取得了令人鼓舞的结果，但在临床推广应用中仍存在一些困难，如何确保抗肿瘤免疫效应物可以大量扩增并能在体内长时间停留，如何选择性杀伤肿瘤细胞以及确保应用安全等一系列关键问题仍亟待解决。

关键词: 肿瘤, 免疫疗法, CIK细胞

Abstract: Cytokineinduced killer (CIK) cells play important roles in the treatment of solid tumors. In particular, they have broad application prospects for the patients with recurrence or metastasis. Although recently CIK treatment strategy has achieved encouraging results in preclinical studies, there are still some difficulties in the clinical applications. Some key issues remain to be resolved, such as how to ensure that the antitumor immune effector can be a lot of amplified and can stay longer in the body, how to selectively kill tumor cells, and how to ensure the security of application.

Key words: Neoplasms, Immunotherapy, CIK cells

舒心,汪治宇. CIK细胞及其在肿瘤治疗中的应用[J]. 国际肿瘤学杂志, 2015, 42(2): 130-133.

Shu Xin, Wang Zhiyu. CIK cells and their application in the tumor treatment[J]. Journal of International Oncology, 2015, 42(2): 130-133.

参考文献

［1］ Bonanno G, Iudicone P, Mariotti A, et al. Thymoglobulin, interferongamma and interleukin2 efficiently expand cytokineinduced killer (CIK) cells in clinicalgrade cultures［J］. J Transl Med, 2010, 8: 129. ［2］ Rettinger E, Kuci S, Naumann I, et al. The cytotoxic potential of interleukin15stimulated cytokineinduced killer cells against leukemia cells［J］. Cytotherapy, 2011, 14(1): 91-103. ［3］ Todorovic M, Mesiano G, Gammaitoni L, et al. Ex vivo allogeneic stimulation significantly improves expansion of cytokineinduced killer cells without increasing their alloreactivity across HLA barriers［J］. J Immunother, 2012, 35(7): 579-586. ［4］ Introna M, Borleri G, Conti E, et al. Repeated infusions of donorderived cytokineinduced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase Ⅰ study［J］. Haematologica, 2007, 92(7): 952-959. ［5］ Pievani A, Borleri G, Pende D, et al. Dualfunctional capability of CD3+CD56+ CIK cells, a Tcell subset that acquires NK function and retains TCRmediated specific cytotoxicity［J］. Blood, 2011, 118(12): 3301-3310. ［6］ Laport GG, Sheehan K, Baker J, et al. Adoptive immunotherapy with cytokineinduced killer cells for patients with relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation［J］. Biol Blood Marrow Transplant, 2011, 17(11): 1679-1687. ［7］ Kuci S, Rettinger E, Voss B, et al. Efficient lysis of rhabdomyosarcoma cells by cytokineinduced killer cells: implications for adoptive immunotherapy after allogeneic stem cell transplantation［J］. Haematologica, 2010, 95(9): 1579-1586. ［8］ Finke S, Trojaneck B, Lefterova P, et al. Increase of proliferation rate and enhancement of antitumor cytotoxicity of expanded human CD3+ CD56+ immunologic effector cells by receptormediated transfection with the interleukin7 gene［J］. Gene Ther, 1998, 5(1): 31-39. ［9］ Nagaraj S, Ziske C, SchmidtWolf IG. Human cytokineinduced killer cells have enhanced in vitro cytolytic activity via nonviral interleukin2 gene transfer［J］. Genet Vaccines Ther, 2004, 2(1): 12. ［10］ Kim HM, Lim J, Park SK, et al. Antitumor activity of cytokineinduced killer cells against human lung cancer［J］. Int Immunopharmacol, 2007, 7(13): 1802-1807. ［11］ Wongkajornsilp A, Somchitprasert T, Butraporn R, et al. Human cytokineinduced killer cells specifically infiltrated and retarded the growth of the inoculated human cholangiocarcinoma cells in SCID mice［J］. Cancer Invest, 2009, 27(2): 140-148. ［12］ Kim HM, Kang JS, Lim J, et al. Antitumor activity of cytokineinduced killer cells in nude mouse xenograft model［J］. Arch Pharm Res, 2009, 32(5): 781-787. ［13］ Chan JK, Hamilton CA, Cheung MK, et al. Enhanced killing of primary ovarian cancer by retargeting autologous cytokineinduced killer cells with bispecific antibodies: a preclinical study［J］. Clin Cancer Res, 2006, 12(6): 1859-1867. ［14］ Sangiolo D, Mesiano G, Cammarata C, et al. Effective preclinical adoptive immunotherapy with cytokineinduced killer cells for bone sarcomas.［J］. Bone Marrow Transplantation,2011,46:87. ［15］ SchmidtWolf IG, Finke S, Trojaneck B, et al. Phase Ⅰ clinical study applying autologous immunological effector cells transfected with the interleukin2 gene in patients with metastatic renal cancer, colorectal cancer and lymphoma［J］. Br J Cancer, 1999, 81(6): 1009-1016. ［16］ Olioso P, Giancola R, Di Riti M, et al. Immunotherapy with cytokine induced killer cells in solid and hematopoietic tumours: a pilot clinical trial［J］. Hematol Oncol, 2009, 27(3): 130-139. ［17］ Hui D, Qiang L, Jian W, et al. A randomized, controlled trial of postoperative adjuvant cytokineinduced killer cells immunotherapy after radical resection of hepatocellular carcinoma［J］. Dig Liver Dis, 2009, 41(1): 36-41. ［18］ Weng DS, Zhou J, Zhou QM, et al. Minimally invasive treatment combined with cytokineinduced killer cells therapy lower the shortterm recurrence rates of hepatocellular carcinomas［J］. J Immunother, 2008, 31(1): 63-71. ［19］ Jiang JT, Shen YP, Wu CP, et al. Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients［J］. World J Gastroenterol, 2010, 16(48): 6155-6162. ［20］ Liu L, Zhang W, Qi X, et al. Randomized study of autologous cytokineinduced killer cell immunotherapy in metastatic renal carcinoma［J］. Clin Cancer Res, 2012, 18(6): 1751-1759. ［21］ Hontscha C, Borck Y, Zhou H, et al. Clinical trials on CIK cells: first report of the international registry on CIK cells (IRCC)［J］. J Cancer Res Clin Oncol, 2011, 137(2): 305-310. ［22］ Marin V, Kakuda H, Dander E, et al. Enhancement of the antileukemic activity of cytokine induced killer cells with an antiCD19 chimeric receptor delivering a 41BBzeta activating signal［J］. Exp Hematol, 2007, 35(9): 1388-1397. ［23］ Thompson JA, Hamid O, Minor D, et al. Ipilimumab in treatmentnaive and previously treated patients with metastatic melanoma: retrospective analysis of efficacy and safety data from a phase Ⅱ trial［J］. J Immunother, 2012, 35(1): 73-77.

[1]	刘娜, 寇介丽, 杨枫, 刘桃桃, 李丹萍, 韩君蕊, 杨立洲. 血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值[J]. 国际肿瘤学杂志, 2024, 51(6): 321-325.
[2]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊. 局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[3]	袁健, 黄燕华. Hp-IgG抗体联合血清DKK1、sB7-H3对早期胃癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(6): 338-343.
[4]	陈红健, 张素青. 血清miR-24-3p、H2AFX与肝癌患者临床病理特征及术后复发的关系研究[J]. 国际肿瘤学杂志, 2024, 51(6): 344-349.
[5]	郭泽浩, 张俊旺. PFDN及其亚基在肿瘤发生发展中的作用[J]. 国际肿瘤学杂志, 2024, 51(6): 350-353.
[6]	张百红, 岳红云. 新作用机制的抗肿瘤药物进展[J]. 国际肿瘤学杂志, 2024, 51(6): 354-358.
[7]	许凤琳, 吴刚. EBV在鼻咽癌肿瘤免疫微环境和免疫治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 359-363.
[8]	王盈, 刘楠, 郭兵. 抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[9]	张蕊, 褚衍六. 基于FIT与肠道菌群的结直肠癌风险评估模型的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 370-375.
[10]	高凡, 王萍, 杜超, 褚衍六. 肠道菌群与结直肠癌非手术治疗的相关研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 376-381.
[11]	王丽, 刘志华, 杨伟洪, 蒋凤莲, 李全泳, 宋浩杰, 鞠文东. ROS1突变肺腺鳞癌合并脑梗死为主要表现的Trousseau综合征1例[J]. 国际肿瘤学杂志, 2024, 51(6): 382-384.
[12]	范志鹏, 余静, 胡静, 廖正凯, 徐禹, 欧阳雯, 谢丛华. 炎症标志物的变化趋势对一线接受免疫联合化疗的晚期非小细胞肺癌患者预后的预测价值[J]. 国际肿瘤学杂志, 2024, 51(5): 257-266.
[13]	刘静, 刘芹, 黄梅. 基于SMOTE算法的食管癌放化疗患者肺部感染的预后模型构建[J]. 国际肿瘤学杂志, 2024, 51(5): 267-273.
[14]	杨琳, 路宁, 温华, 张明鑫, 朱琳. 炎症负荷指数与胃癌临床关系研究[J]. 国际肿瘤学杂志, 2024, 51(5): 274-279.
[15]	王俊毅, 洪楷彬, 纪荣佳, 陈大朝. 癌结节对结直肠癌根治性切除术后肝转移的影响[J]. 国际肿瘤学杂志, 2024, 51(5): 280-285.