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CRISPR/CAS9基因组编辑在基于T细胞的癌症免疫治疗中的治疗潜力

Therapeutic potential of CRISPR/CAS9 genome modification in T cell-based immunotherapy of cancer.

作者信息

Kavousinia Pegah, Ahmadi Mohammad Hossein, Sadeghian Hamid, Hosseini Bafghi Mahdi

机构信息

Department of Laboratory Sciences, Faculty of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Laboratory Sciences, Faculty of Paramedical and Rehabilitation Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Cytotherapy. 2024 May;26(5):436-443. doi: 10.1016/j.jcyt.2024.02.014. Epub 2024 Feb 23.

DOI:10.1016/j.jcyt.2024.02.014
PMID:38466263
Abstract

Today, genome editing technologies like zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR) are being used in clinical trials and the treatment of diseases like acquired immunodeficiency syndrome (AIDS) and cancer. CRISPR stands out as one of the most advanced tools for genome editing due to its simplicity and cost-effectiveness. It can selectively modify specific locations in the genome, offering new possibilities for treating human diseases. The CRISPR system uses ribonucleic acid-deoxyribonucleic acid (RNA-DNA) recognition to combat infections, regulate gene expression, and treat cancer. Chimeric antigen receptor (CAR) T-cell therapy, which uses T lymphocytes to eliminate cancer cells, can be improved by combining it with CRISPR technology. However, there are challenges in using CAR-T cells, including a lack of quantity and quality, exhaustion, neurotoxicity, cytokine release syndrome (CRS), B cell aplasia, tumor lysis syndrome, and anaphylaxis. Preclinical studies on CRISPR-edited CAR-T cells show promising results and targeting detrimental regulatory genes can enhance cancer treatment in the future.

摘要

如今,诸如锌指核酸酶(ZFNs)、转录激活样效应因子核酸酶(TALENs)和成簇规律间隔短回文重复序列(CRISPR)等基因组编辑技术正被用于临床试验以及治疗诸如获得性免疫缺陷综合征(艾滋病)和癌症等疾病。CRISPR因其简单性和成本效益而成为基因组编辑最先进的工具之一。它可以选择性地修饰基因组中的特定位置,为治疗人类疾病提供了新的可能性。CRISPR系统利用核糖核酸 - 脱氧核糖核酸(RNA - DNA)识别来对抗感染、调节基因表达和治疗癌症。嵌合抗原受体(CAR)T细胞疗法利用T淋巴细胞消除癌细胞,将其与CRISPR技术相结合可以得到改进。然而,使用CAR - T细胞存在挑战,包括数量和质量不足、耗竭、神经毒性、细胞因子释放综合征(CRS)、B细胞发育不全、肿瘤溶解综合征和过敏反应。对CRISPR编辑的CAR - T细胞的临床前研究显示出有前景的结果,并且靶向有害的调节基因未来可以增强癌症治疗效果。

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