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借助CRISPR系统改进基于CAR T细胞的免疫疗法的新进展。

Novelty in improvement of CAR T cell-based immunotherapy with the aid of CRISPR system.

作者信息

Hajifathali Abbas, Lasemi Maryam Vahdat, Mehravar Maryam, Moshari Mohammad Reza, Alizadeh Afshin Mohammad, Roshandel Elham

机构信息

Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Hematol Transfus Cell Ther. 2024 Jan-Mar;46(1):58-66. doi: 10.1016/j.htct.2023.05.009. Epub 2023 Jul 12.

Abstract

INTRODUCTION

Chimeric Antigen Receptor (CAR) T cells have tremendous potentials for cancer treatment; however, various challenges impede their universal use. These restrictions include the poor function of T cells in tumor microenvironments, the shortage of tumor-specific antigens and, finally, the high cost and time-consuming process, as well as the poor scalability of the method. Creative gene-editing tools have addressed each of these limitations and introduced next generation products for cell therapy. The clustered regularly interspaced short palindromic repeats-associated endonuclease 9 (CRISPR/Cas9) system has triggered a revolution in biology fields, as it has a great capacity for genetic manipulation.

METHOD

In this review, we considered the latest development of CRISPR/Cas9 methods for the chimeric antigen receptor T cell (CAR T)-based immunotherapy.

RESULTS

The ability of the CRISPR/Cas9 system to generate the universal CAR T cells and also potent T cells that are persistent against exhaustion and inhibition was explored.

CONCLUSION

We explained CRISPR delivery methods, as well as addressing safety concerns related to the use of the CRISPR/Cas9 system and their potential solutions.

摘要

引言

嵌合抗原受体(CAR)T细胞在癌症治疗方面具有巨大潜力;然而,各种挑战阻碍了它们的广泛应用。这些限制包括T细胞在肿瘤微环境中的功能不佳、肿瘤特异性抗原的缺乏,以及最终的高成本和耗时的过程,还有该方法的可扩展性差。创新的基因编辑工具已经解决了这些局限性,并推出了用于细胞治疗的下一代产品。成簇规律间隔短回文重复序列相关核酸酶9(CRISPR/Cas9)系统在生物学领域引发了一场革命,因为它具有强大的基因操作能力。

方法

在本综述中,我们探讨了基于嵌合抗原受体T细胞(CAR T)免疫疗法的CRISPR/Cas9方法的最新进展。

结果

研究了CRISPR/Cas9系统产生通用CAR T细胞以及持久抵抗耗竭和抑制的强效T细胞的能力。

结论

我们解释了CRISPR的递送方法,并讨论了与使用CRISPR/Cas9系统相关的安全问题及其潜在解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4da/10935483/ab928dbc78ac/gr1.jpg

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