不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
靶向 CRISPR/Cas9 基因编辑工具重编程免疫系统细胞的创新策略：肿瘤治疗的新时代
英文原题：Innovative Strategies of Reprogramming Immune System Cells by Targeting CRISPR/Cas9-Based Genome-Editing Tools: A New Era of Cancer Management.
查看英文原题
Innovative Strategies of Reprogramming Immune System Cells by Targeting CRISPR/Cas9-Based Genome-Editing Tools: A New Era of Cancer Management.
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中文摘要
近期，成簇规律间隔短回文重复序列/相关蛋白9（CRISPR/Cas9）系统的研究进展推动了基因组编辑技术及其在细胞分化和免疫应答调控中的应用。这项技术也帮助研究人员理解癌症进展机制，并设计新型抗肿瘤免疫疗法。目前常利用CRISPR/Cas9基因组编辑技术工程化通用T细胞，使其表达重组T细胞受体（TCR）或嵌合抗原受体（CAR）。
此外，该技术还用于细胞因子刺激、抗体设计、自然杀伤（NK）细胞转移及克服免疫检查点。CRISPR/Cas9在构建过继细胞转移（ACT）免疫治疗基础元件方面的创新潜力，为抗肿瘤免疫治疗开辟了新途径，其中部分疗法已获FDA批准。对免疫遗传调节因子的改造，为免疫肿瘤学中设计、实施和解读CRISPR/Cas9筛选提供了新方向。淋巴瘤、黑色素瘤、肺癌和肝癌等多种曾被认为难以治疗的癌症，已采用该策略开展治疗。如何安全且有效地将CRISPR/Cas9递送至免疫细胞仍是实现高效免疫治疗的挑战。已有病毒介导、电穿孔、显微注射和纳米制剂等多种靶向方法，但各自存在局限。本文综述CRISPR/Cas9技术与免疫治疗结合用于癌症管理的最新进展，并详细介绍将该基因编辑系统递送至免疫细胞、以重编程免疫系统并作为新型抗癌免疫治疗策略的创新方法，同时讨论未来前景和临床试验。
展开英文摘要原文
The recent developments in the study of clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) system have revolutionized the art of genome-editing and its applications for cellular differentiation and immune response behavior.
This technology has further helped in understanding the mysteries of cancer progression and possible designing of novel antitumor immunotherapies. CRISPR/Cas9-based genome-editing is now often used to engineer universal T-cells, equipped with recombinant T-cell receptor (TCR) or chimeric antigen receptor (CAR).
In addition, this technology is used in cytokine stimulation, antibody designing, natural killer (NK) cell transfer, and to overcome immune checkpoints. The innovative potential of CRISPR/Cas9 in preparing the building blocks of adoptive cell transfer (ACT) immunotherapy has opened a new window of antitumor immunotherapy and some of them have gained FDA approval. The manipulation of immunogenetic regulators has opened a new interface for designing, implementation and interpretation of CRISPR/Cas9-based screening in immuno-oncology.
Several cancers like lymphoma, melanoma, lung, and liver malignancies have been treated with this strategy, once thought to be impossible. The safe and efficient delivery of CRISPR/Cas9 system within the immune cells for the genome-editing strategy is a challenging task which needs to be sorted out for efficient immunotherapy. Several targeting approaches like virus-mediated, electroporation, microinjection and nanoformulation-based methods have been used, but each procedure offers some limitations.
Here, we elaborate the recent updates of cancer management through immunotherapy in partnership with CRISPR/Cas9 technology.
Further, some innovative methods of targeting this genome-editing system within the immune system cells for reprogramming them, as a novel strategy of anticancer immunotherapy is elaborated.
In addition, future prospects and clinical trials are also discussed.
论文信息
- 作者
- Allemailem KS、Alsahli MA、Almatroudi A、Alrumaihi F、Al Abdulmonem W、Moawad AA、Alwanian WM、Almansour NM
- 第一作者单位
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.Saudi Arabia
- 通讯作者单位
- Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.Saudi Arabia
- 文献类型
- 综述
- 期刊
- International journal of nanomedicine2023
- 原文标识
- PubMed 37795042 · DOI 10.2147/IJN.S424872
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