CRISPR/Cas9技术在CAR-T细胞治疗肿瘤中作用的研究进展

doi:10.16352/j.issn.1001-6325.2023.08.1313

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (8): 1313-1316.doi: 10.16352/j.issn.1001-6325.2023.08.1313

CRISPR/Cas9技术在CAR-T细胞治疗肿瘤中作用的研究进展

伍琦, 王绍波^*

昆明理工大学附属医院云南省第一人民医院 PET/CT中心,云南昆明 650032

收稿日期:2022-03-10 修回日期:2023-01-06 出版日期:2023-08-05 发布日期:2023-07-26
通讯作者: ^*15812082912@126.com
基金资助:
国家自然科学基金(81760306);云南省卫生高层次人才(医学学科带头人)(D-2018011);云南省“万人计划”青年拔尖人才项目(YNWR-QNBJ-2018-243)

Progress in CRISPR/Cas9 for CAR-T cell therapy of tumors

WU Qi, WANG Shaobo^*

PET/CT Center, the Affiliated Hospital of Kunming University of Science and Technology, the First People's Hospital of Yunnan Province, Kunming 650032, China

Received:2022-03-10 Revised:2023-01-06 Online:2023-08-05 Published:2023-07-26
Contact: ^*15812082912@126.com

摘要/Abstract

摘要： CRISPR/Cas9基因编辑技术能有效解决嵌合抗原受体T细胞(CAR-T)疗法中T细胞来源不足的问题,并通过敲除T细胞活性抑制的相关基因,增强其肿瘤杀伤作用。此外,该技术还可用于构建具有双重靶向作用的T细胞,阻止肿瘤免疫逃逸,减少治疗后复发、耐药等情况的发生。相较于其他基因工程技术的复杂过程,CRISPR/Cas9具有便捷高效及多重基因组编辑的优点,对完善CAR-T治疗策略具有重要意义。

关键词: 嵌合抗原受体T细胞, CRISPR/Cas9, 免疫治疗

Abstract: CRISPR/Cas9 gene editing technology can effectively solve the problem of insufficient source of T cells in chimerical antigen receptor-T (CAR-T) therapy and enhance their anti-tumor abilities by knocking out the genes related to the suppression of T cells activity. The technology can also be used to construct T cells with dual-targeting effect to stop tumor immune escape and inhibit recurrence and drug resistance development during chemotherapy. Compared with the other genetic engineering technologies that have complex processes, multiple genome editing by CRISPR/Cas9 is a technology of efficient and convenient to operate.So it is believed to be valuable and potential target molecules for CAR-T therapy.

Key words: CAR-T cells, CRISPR/Cas9, immunotherapy

中图分类号:

伍琦, 王绍波. CRISPR/Cas9技术在CAR-T细胞治疗肿瘤中作用的研究进展[J]. 基础医学与临床, 2023, 43(8): 1313-1316.

WU Qi, WANG Shaobo. Progress in CRISPR/Cas9 for CAR-T cell therapy of tumors[J]. Basic & Clinical Medicine, 2023, 43(8): 1313-1316.

参考文献 25

[1]	Zhou X, Tu S, Wang C, et al. Phase Ⅰ trial of fourth-generation anti-CD19 chimeric antigen receptor T cells against relapsed or refractory B cell non-Hodgkin lymphomas[J]. Front Immunol, 2020, 11: 564099. doi: 10.3389/fimmu.2020.564099.
[2]	Roddie C, Dias J, O'Reilly MA, et al. Durable responses and low toxicity after fast off-rate CD19 chimeric antigen receptor-T therapy in adults with relapsed or refractory B-cell acute lymphoblastic leukemia[J]. J Clin Oncol, 2021, 39: 3352-3363.
[3]	Haas AR, Tanyi JL, O'Hara MH, et al. Phase Ⅰ study of lentiviral-transduced chimeric antigen receptor-modified T cells recognizing mesothelin in advanced solid cancers[J]. Mol Ther, 2019, 27: 1919-1929.
[4]	Adusumilli PS, Zauderer MG, Rivière I, et al. A phase Ⅰ trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease, in combination with the anti-PD-1 agent pembrolizumab[J]. Cancer Discov, 2021, 11: 2748-2763.
[5]	Heczey A, Courtney AN, Montalbano A, et al. Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis[J]. Nat Med, 2020, 26: 1686-1690.
[6]	Katz SC, Hardaway J, Prince E, et al. HITM-SIR: phase Ib trial of intraarterial chimeric antigen receptor T-cell therapy and selective internal radiation therapy for CEA(+) liver metastases[J]. Cancer Gene Ther, 2020, 27: 341-355.
[7]	Zhang Y, Zhang Z, Ding Y, et al. Phase I clinical trial of EGFR-specific CAR-T cells generated by the piggyBac transposon system in advanced relapsed/refractory non-small cell lung cancer patients[J]. J Cancer Res Clin Oncol, 2021, 147: 3725-3734.
[8]	Liu Y, Guo Y, Wu Z, et al. Anti-EGFR chimeric antigen receptor-modified T cells in metastatic pancreatic carcinoma: a phase Ⅰ clinical trial[J]. Cytotherapy, 2020, 22: 573-580.
[9]	Wang Q, Zhong X, Li Q, et al. CRISPR-Cas9-mediated in vivo gene integration at the albumin locus recovers hemostasis in neonatal and adult hemophilia B mice[J]. Mol Ther Methods Clin Dev, 2020, 18: 520-531.
[10]	Guo P, Yang J, Huang J, et al. Therapeutic genome editing of triple-negative breast tumors using a noncationic and deformable nanolipogel[J]. Proc Natl Acad Sci U S A, 2019, 116: 18295-18303.
[11]	Ren J, Liu X, Fang C, et al. Multiplex genome editing to generate universal CAR T cells resistant to PD1 inhibition[J]. Clin Cancer Res, 2017, 23: 2255-2266.
[12]	Eyquem J, Mansilla-Soto J, Giavridis T, et al. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection[J]. Nature, 2017, 543: 113-117.
[13]	Hu W, Zi Z, Jin Y, et al. CRISPR/Cas9-mediated PD-1 disruption enhances human mesothelin-targeted CAR T cell effector functions[J]. Cancer Immunol Immunother, 2019, 68: 365-377.
[14]	Ruste V, Goldschmidt V, Laparra A, et al. The determinants of very severe immune-related adverse events associated with immune checkpoint inhibitors: a prospective study of the French REISAMIC registry[J]. Eur J Cancer, 2021, 158: 217-224.
[15]	Gargett T, Yu W, Dotti G, et al. GD2-specific CAR T cells undergo potent activation and deletion following antigen encounter but can be protected from activation-induced cell death by PD-1 blockade[J]. Mol Ther, 2016, 24: 1135-1149.
[16]	Zhang Y, Zhang X, Cheng C, et al. CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells[J]. Front Med, 2017, 11: 554-562.
[17]	Giuffrida L, Sek K, Henderson MA, et al. CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy [J]. Nat Commun, 2021, 12: 3236. doi: 10.1038/s41467-021-23331-5.
[18]	Jung IY, Kim YY, Yu HS, et al. CRISPR/Cas9-mediated knockout of DGK improves antitumor activities of human T cells[J]. Cancer Res, 2018, 78: 4692-4703.
[19]	Sterner RM, Sakemura R, Cox MJ, et al. GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts[J]. Blood, 2019, 133: 697-709.
[20]	Liu S, Deng B, Yin Z, et al. Combination of CD19 and CD22 CAR-T cell therapy in relapsed B-cell acute lymphoblastic leukemia after allogeneic transplantation[J]. Am J Hematol, 2021, 96: 671-679.
[21]	Liu Y, Deng B, Hu B, et al. Sequential different B-cell antigen-targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt lymphoma[J]. Blood Adv, 2022, 6: 717-730.
[22]	Dai H, Wu Z, Jia H, et al. Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia[J]. J Hematol Oncol, 2020, 13: 30. doi: 10.1186/s13045-020-00856-8.
[23]	Cordoba S, Onuoha S, Thomas S, et al. CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial[J]. Nat Med, 2021, 27: 1797-1805.
[24]	Hu Y, Zhou Y, Zhang M, et al. CRISPR/Cas9-engineered universal CD19/CD22 dual-targeted CAR-T cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia[J]. Clin Cancer Res, 2021, 27: 2764-2772.
[25]	Zanetti SR, Velasco-Hernandez T, Gutierrez-Agüera F, et al. A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL[J]. Mol Ther, 2022, 30: 550-563.

CRISPR/Cas9技术在CAR-T细胞治疗肿瘤中作用的研究进展

Progress in CRISPR/Cas9 for CAR-T cell therapy of tumors

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 25

相关文章 15

编辑推荐

Metrics

本文评价

[1]	刘宛榕, 赵林. 颅内生殖细胞肿瘤的药物治疗[J]. 基础医学与临床, 2024, 44(10): 1350-1356.
[2]	葛郁平, 刘莹, 赵林. 血管肉瘤药物治疗进展[J]. 基础医学与临床, 2024, 44(10): 1363-1367.
[3]	杨俊豪, 赵林. 恶性间皮瘤的靶向与免疫治疗[J]. 基础医学与临床, 2024, 44(10): 1342-1349.
[4]	颜晨红, 金儿. 外泌体PD-L1在非小细胞肺癌诊断和治疗上的研究进展[J]. 基础医学与临床, 2023, 43(9): 1457-1461.
[5]	代娣, 刘玉琴. 原发性胃淋巴瘤的诊断难点及治疗进展[J]. 基础医学与临床, 2023, 43(9): 1462-1466.
[6]	陈忠婕, 黄嘉如, 胡清, 赵珍琴, 陈俏俏, 孙浚源, 贾静. 免疫检查点CD276蛋白参与肿瘤发生发展作用机制的研究进展[J]. 基础医学与临床, 2023, 43(7): 1143-1147.
[7]	李珍, 段昭君, 罗云萍. 神经节苷脂GD2可作为肺癌干细胞一个潜在的候选标志物[J]. 基础医学与临床, 2023, 43(5): 777-784.
[8]	赵永晶, 仇佳星, 张迪雅, 郭泓江, 王钰铖, 鞠瑞, 郭磊. 稳定敲除Mcart-1下调RAW264.7巨噬细胞增殖能力和氧化磷酸化水平[J]. 基础医学与临床, 2023, 43(4): 568-575.
[9]	李晓光, 杨璐, 刘旭东, 贾鑫淼, 杨欣壮, 崔丽英. 基因治疗肌萎缩侧索硬化机制的研究进展[J]. 基础医学与临床, 2023, 43(4): 674-679.
[10]	周岚, 张生贵, 胡祖梁, 王添贤, 岳鹏鹏, 于鸿浩. 基于CRISPR/Cas9系统高效编辑小鼠miR let-7a[J]. 基础医学与临床, 2022, 42(6): 857-863.
[11]	郭晓鹏, 幸兵, 马文斌. 垂体腺瘤免疫微环境及免疫治疗的研究进展[J]. 基础医学与临床, 2022, 42(1): 173-178.
[12]	岳鹏鹏, 黎成钦, 农月娟, 陈玲, 付灿, 于鸿浩. 构建模拟人致病位点突变的靶向小鼠Krt14的CRISPR/Cas9系统[J]. 基础医学与临床, 2021, 41(3): 325-332.
[13]	李倩, 刘纯华, 王晨怡, 谈娇娇, 马玉萍, 吕海宏. 炎性因子调控1型糖尿病血管内皮细胞功能的研究进展[J]. 基础医学与临床, 2021, 41(10): 1497-1501.
[14]	孙靖玉, 姚赫, 胡刚, 魏洁, 郭君, 张鑫, 林雅军. CRISPR/Cas9介导下敲除KNDC1的人脐静脉内皮细胞具有抗衰老能力[J]. 基础医学与临床, 2020, 40(9): 1175-1181.
[15]	韩玲, 杨科, 薛征, 吕湘. 通过阵列式标签高通量测序高效鉴定点突变单克隆细胞[J]. 基础医学与临床, 2020, 40(7): 903-911.