提高CAR-T细胞疗法抗癌活性及安全性的研究进展

夏涌; 黄健; 钱其军

doi:10.3969/j.issn.1006-0111.2016.04.023

提高CAR-T细胞疗法抗癌活性及安全性的研究进展

doi: 10.3969/j.issn.1006-0111.2016.04.023

1.
Department of Biotherapy, Eastern Hepatobiliary Surgical Hospital affliated to Second Military Medical University, Shanghai 200438, China
2.
第二军医大学附属东方肝胆外科医院生物治疗科, 上海 200438

Research progress on improving the anti-cancer activity and safety of the CAR-T cells therapy

1.
Department of Biotherapy, Eastern Hepatobiliary Surgical Hospital affliated to Second Military Medical University, Shanghai 200438, China
2.
the Third Department of Hepatic surgery, Eastern Hepatobiliary Surgical Hospital affliated to Second Military Medical University, Shanghai 200438, China

摘要: 经过25年的研究，以嵌合抗原受体（CAR）为基础的细胞治疗目前在治疗恶性肿瘤方面展现了巨大潜力。近几年有大量的相关试验和临床数据被报道，本综述通过对这些数据的对比和分析，讨论如何增强CAR-T细胞疗法对不可切除的恶性肿瘤的治疗效果，也对CAR-T细胞技术在恶性肿瘤临床治疗领域存在的安全问题及解决策略进行概述。
- 嵌合抗原受体 /
- 过继细胞免疫治疗 /
- 肿瘤
Abstract: The great potential of cell therapy based on chimeric antigen receptor (CAR) has been demonstrated in the treatment of malignant tumors through 25 years of research.A large number of experimental and clinical data have been reported in recent years.This review compares and analyzes these data to discuss how to enhance the efficacy of CAR-T cell therapy in the treatment of unresectable malignant tumors and to summarize the safety issues and solution strategies of CAR-T cell technology in the treatment of malignant tumors.
- chimeric antigen receptor (CAR) /
- adoptive cell immunotherapy /
- tumors

[1]	Maus MV, Grupp SA, Porter DL, June CH. Antibody-modified T cells:CARs take the front seat forhematologic malignancies[J]. Blood, 2014, 123(17):2625-2635.
[2]	陈杰, 王宇环, 罗成林, 等. 嵌合抗原受体T细胞介绍及抗肿瘤临床应用[J]. 中国细胞生物学学报, 2014, 36(2):228-235.
[3]	张少华,毕经旺. 嵌合抗原受体修饰T细胞在恶性肿瘤中的研究进展[J]. 国际肿瘤学杂志,2014,41(7):495-499.
[4]	Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia[J]. N Engl J Med,2014,371(16):1507-1517.
[5]	徐云云, 金润铭. 血液肿瘤治疗中嵌合抗原受体基因修饰T淋巴细胞作用[J]. 中国实用儿科杂志,2013,28(8):626-629.
[6]	Louis CU, Savoldo B, Dotti G, et al. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma[J].Blood,2011,118(23):6050-6056.
[7]	Lamers CH, Sleijfer S, van Steenbergen S, et al. Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells:clinical evaluation and management of on-target toxicity[J]. Mol Ther,2013,21(4):904-912.
[8]	Rizvi NA, Mazières J, Planchard D, et al.Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063):a phase 2,single-arm trial[J]. Lancet Oncol,2015, 16(3):257-265.
[9]	Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance[J]. Nature, 2014,515(7528):568-571.
[10]	Rozali EN, Hato SV, Robinson BW, et al. Programmed death ligand 2 in cancer-induced immune suppression[J]. Clin Dev Immunol,2012,2012:656340.
[11]	John LB, Devaud C, Duong CP, et al. Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells[J]. Clin Cancer Res,2013,19(20):5636-5646.
[12]	John LB, Kershaw MH, Darcy PK. Blockade of PD-1 immunosuppression boosts CAR T-cell therapy[J]. Oncoimmunology,2013,2(10):e26286.
[13]	Yan Y, Li S, Jia T, et al. Combined therapy with CTL cells and oncolytic adenovirus expressing IL-15-induced enhanced antitumor activity[J].Tumour Biol,2015,36(6):4535-4543.
[14]	Nishio N, Diaconu I, Liu H, et al. Armed oncolytic virus enhances immune functions of chimeric antigen receptor-modified T cells in solid tumors[J].Cancer Res,2014,74(18):5195-5205.
[15]	鹿萍,郝莎, 袁卫平,等.嵌合抗原受体——癌症免疫治疗的新希望[J]. 中华医学杂志,2015,95(4):311-314.
[16]	Long AH, Haso WM, Shern JF, et al. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors[J]. Nat Med,2015,21(6):581-590.
[17]	Song DG, Ye Q, Carpenito C, et al. In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137(4-1BB)[J]. Cancer Res,2011,71(13):4617-4627.
[18]	Zhao Z, Condomines M, van der Stegen SJ, et al. Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells[J]. Cancer Cell,2015,28(4):415-428.
[19]	Prapa M, Caldrer S, Spano C, et al. A novel anti-GD2/4-1BB chimeric antigen receptor triggers neuroblastoma cell killing[J]. Oncotarget,2015,6(28):24884-24894.
[20]	Ahmed N, Brawley VS, Hegde M, et al. Human epidermal growth factor receptor 2(HER2)-specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma[J]. J Clin Oncol,2015,33(15):1688-1696.
[21]	Maus MV, June CH. CARTs on the road for myeloma[J]. Clin Cancer Res,2014,20(15):3899-3901.
[22]	Sadelain M, Brentjens R, Riviere I. The basic principles of chimeric antigen receptor design[J]. Cancer Discov,2013,3(4):388-398.
[23]	Kalaitsidou M, Kueberuwa G, Schutt A, et al. CAR T-cell therapy:toxicity and the relevance of preclinical models[J]. Immunotherapy,2015,7(5):487-497.
[24]	蔡慧, 赵莲君, 邹征云. 嵌合抗原受体基因修饰T淋巴细胞在肿瘤免疫治疗中的研究[J]. 现代肿瘤医学,2014, 22(11):2730-2734.
[25]	Liu X, Jiang S, Fang C, et al. Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice[J]. Cancer Res,2015,75(17):3596-3607.
[26]	Kloss CC, Condomines M, Cartellieri M, et al. Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells[J]. Nat Biotechnol,2013,31(1):71-75.
[27]	Wilkie S, van Schalkwyk MC, Hobbs S, et al. Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling[J]. J Clin Immunol,2012,32(5):1059-1070.
[28]	Caruso HG, Hurton LV, Najjar A, et al. Tuning sensitivity of CAR to EGFR density limits recognition of normal tissue while maintaining potent antitumor activity[J]. Cancer Res,2015,75(17):3505-3518.
[29]	Davila ML, Riviere I, Wang X, et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia[J]. Sci Transl Med,2014,6(224):224-225.
[30]	Wu CY, Roybal KT, Puchner EM, et al. Remote control of therapeutic T cells through a small molecule-gated chimeric receptor[J].Science,2015,350(6258):aab4077.

[1]	田硕, 厉建中. 转录因子ZNF24在肿瘤中的研究进展 . 药学实践与服务, 2023, 41(12): 710-713, 721. doi: 10.12206/j.issn.2097-2024.202204043
[2]	方宇昕, 李育, 刘宝姝, 董国强. 线性泛素连接酶复合体与去线性泛素化酶在肿瘤中的研究进展 . 药学实践与服务, 2023, 41(9): 534-539. doi: 10.12206/j.issn.2097-2024.202307045
[3]	高习清, 卢光照, 鲁莹, 邹豪. 活性氧自由基响应型脂质体在抗肿瘤研究中的应用进展 . 药学实践与服务, 2023, 41(1): 14-17. doi: 10.12206/j.issn.2097-2024.202105086
[4]	丁佳宁, 马进原, 朱全刚. 长链非编码RNA人母系表达基因3在肿瘤发生中作用的研究进展 . 药学实践与服务, 2019, 37(5): 390-393,421. doi: 10.3969/j.issn.1006-0111.2019.05.002
[5]	陈自强, 张玮, 李玉平, 王晓宇. 纳米载药系统逆转肿瘤及骨肉瘤多药耐药的研究进展 . 药学实践与服务, 2016, 34(2): 103-105. doi: 10.3969/j.issn.1006-0111.2016.02.002
[6]	姜文丽, 黄才国. 晚期非小细胞肺癌靶向治疗的研究进展 . 药学实践与服务, 2016, 34(4): 301-304,333. doi: 10.3969/j.issn.1006-0111.2016.04.004
[7]	章浩, 叶真龙, 钱其军. 降低亲和力提高HER2-CAR-T细胞治疗的安全性 . 药学实践与服务, 2016, 34(3): 261-266. doi: 10.3969/j.issn.1006-0111.2016.03.018
[8]	王欢, 佘岚, 王琳召, 马志强, 张欣荣, 杨峰. 氧化介孔碳球纳米粒作为紫杉醇载体的研究 . 药学实践与服务, 2015, 33(2): 114-118. doi: 10.3969/j.issn.1006-0111.2015.02.005
[9]	王欢, 马志强, 杨峰. 用于肿瘤治疗的小分子干扰RNA非病毒载体研究进展 . 药学实践与服务, 2015, 33(6): 498-501. doi: 10.3969/j.issn.1006-0111.2015.06.005
[10]	赵心彬, 倪敏, 陶霞. 他汀类药物多效药理作用及其机制研究进展 . 药学实践与服务, 2013, 31(1): 19-21. doi: 10.3969/j.issn.1006-0111.2013.01.005
[11]	程君, 芮耀诚. 真核延长因子eEF1A功能研究进展 . 药学实践与服务, 2012, 30(2): 89-91,124. doi: 10.3969/j.issn.1006-0111.2012.02.003
[12]	周忻. 50例肿瘤科住院患者的中药用药情况分析 . 药学实践与服务, 2009, 27(1): 55-57.
[13]	章忱, 程康, 郭炜, 卫洪昌. 麝香保心丸对裸小鼠人结肠癌肝转移模型促血管新生因子及肿瘤生长的影响 . 药学实践与服务, 2007, (5): 295-296,302.
[14]	侯雪梅, 崔黎丽, 李国栋, 李卫华. 抗肿瘤药物靶向制剂研究进展 . 药学实践与服务, 2007, (5): 273-275,280.
[15]	丁力, 丁家崇, 郭葆玉. 抗肿瘤药物新靶点半胱天冬酶-10 . 药学实践与服务, 2006, (2): 76-79.
[16]	庞晓军, 黄军章, 刘国勇, 李香乐. 肿瘤基因治疗研究进展 . 药学实践与服务, 2006, (1): 4-6.
[17]	王彦, 刁亚英, 姜远英. ABC转运蛋白与肿瘤多药耐药 . 药学实践与服务, 2003, (1): 28-31.
[18]	王晶, 潘勇华, 王旭明, 刘建飞. 光敏剂及其临床应用进展 . 药学实践与服务, 2002, (2): 67-70.
[19]	范开华, 刘子文, 夏俊. 血卟啉二乙二醇对消化道肿瘤的光动力疗效观察 . 药学实践与服务, 2001, (2): 76-76.
[20]	范开华, 温定量, 周明惠, 夏俊. 2,7,12,18-四甲基-3,8-二(1-甲氧乙基)-13,17-二(3-乙胺基丙基)卟啉衍生物的合成及其光敏活性 . 药学实践与服务, 1999, (6): 344-346.

点击查看大图

计量

文章访问数: 2772
HTML全文浏览量: 316
PDF下载量: 1134
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

留言板

提高CAR-T细胞疗法抗癌活性及安全性的研究进展

doi: 10.3969/j.issn.1006-0111.2016.04.023

Research progress on improving the anti-cancer activity and safety of the CAR-T cells therapy

计量

提高CAR-T细胞疗法抗癌活性及安全性的研究进展

doi: 10.3969/j.issn.1006-0111.2016.04.023

1. Department of Biotherapy, Eastern Hepatobiliary Surgical Hospital affliated to Second Military Medical University, Shanghai 200438, China

2. 第二军医大学附属东方肝胆外科医院生物治疗科, 上海 200438

English Abstract

Research progress on improving the anti-cancer activity and safety of the CAR-T cells therapy

1. Department of Biotherapy, Eastern Hepatobiliary Surgical Hospital affliated to Second Military Medical University, Shanghai 200438, China

2. the Third Department of Hepatic surgery, Eastern Hepatobiliary Surgical Hospital affliated to Second Military Medical University, Shanghai 200438, China

全文HTML

目录

留言板

提高CAR-T细胞疗法抗癌活性及安全性的研究进展

doi: 10.3969/j.issn.1006-0111.2016.04.023

Research progress on improving the anti-cancer activity and safety of the CAR-T cells therapy

计量

出版历程

提高CAR-T细胞疗法抗癌活性及安全性的研究进展

doi: 10.3969/j.issn.1006-0111.2016.04.023

1. Department of Biotherapy, Eastern Hepatobiliary Surgical Hospital affliated to Second Military Medical University, Shanghai 200438, China 2. 第二军医大学附属东方肝胆外科医院生物治疗科, 上海 200438

English Abstract

Research progress on improving the anti-cancer activity and safety of the CAR-T cells therapy

1. Department of Biotherapy, Eastern Hepatobiliary Surgical Hospital affliated to Second Military Medical University, Shanghai 200438, China 2. the Third Department of Hepatic surgery, Eastern Hepatobiliary Surgical Hospital affliated to Second Military Medical University, Shanghai 200438, China

全文HTML

目录

1. Department of Biotherapy, Eastern Hepatobiliary Surgical Hospital affliated to Second Military Medical University, Shanghai 200438, China

2. 第二军医大学附属东方肝胆外科医院生物治疗科, 上海 200438

1. Department of Biotherapy, Eastern Hepatobiliary Surgical Hospital affliated to Second Military Medical University, Shanghai 200438, China

2. the Third Department of Hepatic surgery, Eastern Hepatobiliary Surgical Hospital affliated to Second Military Medical University, Shanghai 200438, China