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优化肿瘤治疗:CAR-T 细胞治疗与 CRISPR/Cas9 的协同潜力

英文原题:Optimizing cancer treatment: the synergistic potential of CAR-T cell therapy and CRISPR/Cas9.

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Optimizing cancer treatment: the synergistic potential of CAR-T cell therapy and CRISPR/Cas9.

PubMed 2024/11/08(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

优化癌症治疗已成为现代肿瘤学的核心目标,免疫治疗和基因工程的发展带来了有前景的新途径。CAR-T 细胞疗法通过利用患者自身免疫细胞靶向并摧毁癌细胞,是一种突破性方法,在急性淋巴细胞白血病(ALL)及其他血液系统恶性肿瘤治疗中取得显著成功。尽管CAR-T 疗法前景良好,但成本高、制备复杂等挑战仍然存在,其治疗实体瘤的疗效也有限。CRISPR/Cas9是一种强效且精准的基因编辑工具;尽管其非预期编辑和脱靶效应带来安全性问题,但与CAR-T 疗法结合具有协同潜力,可望克服上述局限。CRISPR/Cas9可通过提高CAR-T 细胞特异性和持久性、减少脱靶效应,并使细胞能够抵抗肿瘤诱导的免疫抑制,增强CAR-T 疗效。该组合还可敲除免疫检查点抑制因子,从而提高CAR-T 细胞的抗肿瘤活性。近期研究显示,经CRISPR/Cas9编辑的CAR-T 细胞能够靶向以往无法治疗的癌症类型,为难治性癌症患者带来新希望。这种协同策略不仅可提高癌症治疗效力,也为根据个体遗传特征定制治疗方案铺平道路。本综述介绍优化这一策略的研究进展,并探讨其革新更广泛恶性肿瘤治疗的潜力。随着研究不断推进,CAR-T 疗法与CRISPR/Cas9的结合有望改变癌症治疗,使其更加有效且可及。本文综述这一创新治疗策略的当前进展、挑战及未来前景。

展开英文摘要原文

Optimizing cancer treatment has become a pivotal goal in modern oncology, with advancements in immunotherapy and genetic engineering offering promising avenues. CAR-T cell therapy, a revolutionary approach that harnesses the body's own immune cells to target and destroy cancer cells, has shown remarkable success, particularly in treating acute lymphoblastic leukemia (ALL), and in treating other hematologic malignancies. While CAR-T cell therapy has shown promise, challenges such as high cost and manufacturing complexity remain.

However, its efficacy in solid tumors remains limited. The integration of CRISPR/Cas9 technology, a powerful and precise genome-editing tool, also raises safety concerns regarding unintended edits and off-target effects, offers a synergistic potential to overcome these limitations. CRISPR/Cas9 can enhance CAR-T cell therapy by improving the specificity and persistence of CAR-T cells, reducing off-target effects, and engineering resistance to tumor-induced immunosuppression. This combination can also facilitate the knockout of immune checkpoint inhibitors, boosting the anti-tumor activity of CAR-T cells. Recent studies have demonstrated that CRISPR/Cas9-edited CAR-T cells can target previously untreatable cancer types, offering new hope for patients with refractory cancers.

This synergistic approach not only enhances the efficacy of cancer treatment but also paves the way for personalized therapies tailored to individual genetic profiles. This review highlights the ongoing research efforts to refine this approach and explores its potential to revolutionize cancer treatment across a broader range of malignancies.

As research progresses, the integration of CAR-T cell therapy and CRISPR/Cas9 holds the promise of transforming cancer treatment, making it more effective and accessible. This review explores the current advancements, challenges, and future prospects of this innovative therapeutic strategy.

论文信息

作者
Amiri M、Moaveni AK、Majidi Zolbin M、Shademan B、Nourazarian A
第一作者单位
Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.Iran
通讯作者单位
Department of Basic Medical Sciences, Khoy University of Medical Sciences, Khoy, Iran.Iran
文献类型
综述
期刊
Frontiers in immunology2024
原文标识
PubMed 39582866 · DOI 10.3389/fimmu.2024.1462697