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利用 CRISPR/Cas9 技术进行 NK 和 T 细胞免疫治疗的基因工程:意义和挑战。

Genetical engineering for NK and T cell immunotherapy with CRISPR/Cas9 technology: Implications and challenges.

机构信息

Synthetic Biology Engineering Lab of Henan Province, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan Province, PR China.

Synthetic Biology Engineering Lab of Henan Province, School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang, Henan Province, PR China.

出版信息

Cell Immunol. 2021 Nov;369:104436. doi: 10.1016/j.cellimm.2021.104436. Epub 2021 Sep 1.

DOI:10.1016/j.cellimm.2021.104436
PMID:34500148
Abstract

Immunotherapy has become one of the most promising strategies in cancer therapies. Among the therapeutic alternatives, genetically engineered NK/T cell therapies have emerged as powerful and innovative therapeutic modalities for cancer patients with precise targeting and impressive efficacy. Nonetheless, this approach still faces multiple challenges, such as immunosuppressive tumor microenvironment, exhaustion of immune effector cells in tumors, off-target effects manufacturing complexity, and poor infiltration of effector cells, all of which need to be overcome for further utilization to cancers. Recently, CRISPR/Cas9 genome editing technology, with the goal of enhancing the efficacy and increasing the availability of engineered effector cell therapies, has shown considerable potential in the novel strategies and options to overcome these limitations. Here we review the current progress of the applications of CRISPR in cancer immunotherapy. Furthermore, we discuss issues related to the NK/T cell applications, gene delivery methods, efficiency, challenges, and implications of CRISPR/Cas9.

摘要

免疫疗法已成为癌症治疗中最有前途的策略之一。在治疗选择中,经过基因工程改造的自然杀伤 (NK)/T 细胞疗法已经成为癌症患者的一种强大且创新的治疗方式,具有精确靶向和显著疗效。然而,这种方法仍然面临多个挑战,例如免疫抑制性肿瘤微环境、肿瘤中免疫效应细胞的耗竭、制造复杂性、效应细胞浸润不良等,所有这些都需要克服,以便进一步将其应用于癌症治疗。最近,CRISPR/Cas9 基因组编辑技术旨在提高工程效应细胞疗法的疗效和可用性,为克服这些限制提供了新的策略和选择,显示出了相当大的潜力。在这里,我们综述了 CRISPR 在癌症免疫疗法中的应用的最新进展。此外,我们还讨论了与 NK/T 细胞应用、基因传递方法、效率、挑战以及 CRISPR/Cas9 的影响相关的问题。

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