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.

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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

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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

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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

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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