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环状 RNA 在 CAR-T 细胞治疗中推进新一代肿瘤治疗

英文原题:Advancing the next generation of cancer treatment with circular RNAs in CAR-T cell therapy.

查看英文原题

Advancing the next generation of cancer treatment with circular RNAs in CAR-T cell therapy.

PubMed 2024/12/11(内容时间) Biomed Pharmacother

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中文摘要

CAR-T 细胞疗法改变了血液系统恶性肿瘤治疗,但T细胞耗竭、持久性有限及脱靶效应等挑战仍限制其治疗实体瘤的效果。这些问题揭示了当前CAR-T 治疗策略中的关键缺口,尤其是在实体瘤应用方面。环状RNA(circRNA)是一类重要的非编码RNA,具有高度稳定性和精准调控功能,因此有望用于增强下一代CAR-T 疗法。

值得注意的是,circRNA可通过提供创新解决方案克服技术障碍并改善治疗结局,推动临床前研究向临床应用转化。尽管具有潜力,circRNA在CAR-T 细胞治疗实体瘤中的临床应用仍未充分探索,为创新带来重要机会。circRNA调节CAR-T 耗竭、持久性和肿瘤特异性的机制尚未完全阐明;高效、靶向递送circRNA等技术挑战也仍需解决。本综述强调将circRNA整合至CAR-T 疗法的重要性,以提高特异性、减少脱靶效应并改善治疗持久性。通过突出circRNA的创新潜力并指出关键研究空白,本文为推进CAR-T 疗法提供路线图,并为下一代个体化癌症治疗奠定基础。

展开英文摘要原文

Chimeric Antigen Receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies.

However, its effectiveness against solid tumors remains constrained by challenges such as T-cell exhaustion, limited persistence, and off-target effects. These challenges highlight critical gaps in current CAR-T cell therapeutic strategies, particularly for solid tumor applications. Circular RNAs (circRNAs) represent a transformative class of non-coding RNAs, known for their exceptional stability and precise regulatory functions, positioning them as promising candidates for enhancing next-generation CAR-T cell therapies.

Notably, circRNAs can bridge the gap between preclinical research and clinical application by offering innovative solutions to overcome technical hurdles and improve therapeutic outcomes. Despite their potential, circRNAs remain underexplored in clinical application of CAR-T cell therapies for solid tumors, presenting a significant opportunity for innovation. The mechanisms through which circRNAs modulate CAR-T cell exhaustion, persistence, and tumor specificity are not yet fully understood, and technical challenges, such as achieving efficient and targeted circRNA delivery, which still need to be addressed.

This review highlights the importance of integrating circRNAs into CAR-T cell therapy to enhance specificity, minimize off-target effects, and improve therapeutic durability. By emphasizing the innovative potential of circRNAs and identifying key research gaps, this review provides a roadmap for advancing CAR-T cell therapy and setting the stage for the next generation of personalized cancer treatments.

论文信息

作者
Huang S、Xu J、Baran N、Ma W
第一作者单位
Department of Hepatobiliary and Pancreatic Surgery, The First People's Hospital of Huzhou, The First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang 313000, China. Electronic address: hsx_x1974@163.com.China
通讯作者单位
Department of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: wma@health.ucsd.edu.United States
文献类型
综述
期刊
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2024 Dec
原文标识
PubMed 39667221 · DOI 10.1016/j.biopha.2024.117753