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CRISPR/Cas9技术在癌症免疫治疗中的应用:现状与问题

The Application of CRISPR/Cas9 Technology for Cancer Immunotherapy: Current Status and Problems.

作者信息

Wang Luyao, Chen Yurong, Liu Xinrui, Li Ziyi, Dai Xiangpeng

机构信息

Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, First Hospital, Jilin University, Changchun, China.

National-Local Joint Engineering Laboratory of Animal Models for Human Disease, First Hospital, Jilin University, Changchun, China.

出版信息

Front Oncol. 2022 Jan 17;11:704999. doi: 10.3389/fonc.2021.704999. eCollection 2021.

Abstract

Cancer is one of the main causes of disease-related deaths in the world. Although cancer treatment strategies have been improved in recent years, the survival time of cancer patients is still far from satisfied. Cancer immunotherapy, such as Oncolytic virotherapy, Immune checkpoints inhibition, Chimeric antigen receptor T (CAR-T) cell therapy, Chimeric antigen receptor natural killer (CAR-NK) cell therapy and macrophages genomic modification, has emerged as an effective therapeutic strategy for different kinds of cancer. However, many patients do not respond to the cancer immunotherapy which warrants further investigation to optimize this strategy. The clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9), as a versatile genome engineering tool, has become popular in the biology research field and it was also applied to optimize tumor immunotherapy. Moreover, CRISPR-based high-throughput screening can be used in the study of immunomodulatory drug resistance mechanism. In this review, we summarized the development as well as the application of CRISPR/Cas9 technology in the cancer immunotherapy and discussed the potential problems that may be caused by this combination.

摘要

癌症是全球疾病相关死亡的主要原因之一。尽管近年来癌症治疗策略有所改进,但癌症患者的生存时间仍远不尽人意。癌症免疫疗法,如溶瘤病毒疗法、免疫检查点抑制、嵌合抗原受体T(CAR-T)细胞疗法、嵌合抗原受体自然杀伤(CAR-NK)细胞疗法和巨噬细胞基因组修饰,已成为针对不同类型癌症的有效治疗策略。然而,许多患者对癌症免疫疗法没有反应,这就需要进一步研究以优化该策略。成簇规律间隔短回文重复序列及其相关蛋白9(CRISPR/Cas9)作为一种通用的基因组工程工具,在生物学研究领域已变得流行起来,并且它也被应用于优化肿瘤免疫疗法。此外,基于CRISPR的高通量筛选可用于免疫调节耐药机制的研究。在本综述中,我们总结了CRISPR/Cas9技术在癌症免疫疗法中的发展及应用,并讨论了这种联合可能引起的潜在问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c6c6/8801488/9516c63122b5/fonc-11-704999-g001.jpg

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