Huang Sanxiong, Xu Juling, Baran Natalia, Ma Wenxue
Department of Hepatobiliary and Pancreatic Surgery, The First People's Hospital of Huzhou, The First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang 313000, China.
Department of Surgical Teaching and Research, Huzhou University School of Medicine, Huzhou, Zhejiang 313000, China.
Biomed Pharmacother. 2024 Dec;181:117753. doi: 10.1016/j.biopha.2024.117753. Epub 2024 Dec 11.
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.
嵌合抗原受体T细胞（CAR-T）疗法彻底改变了血液系统恶性肿瘤的治疗方式。然而，其对实体瘤的有效性仍受到诸如T细胞耗竭、持久性有限和脱靶效应等挑战的限制。这些挑战凸显了当前CAR-T细胞治疗策略中的关键差距，特别是在实体瘤应用方面。环状RNA（circRNA）代表了一类具有变革性的非编码RNA，以其卓越的稳定性和精确的调控功能而闻名，使其成为增强下一代CAR-T细胞疗法的有希望的候选者。值得注意的是，circRNA可以通过提供创新解决方案来克服技术障碍并改善治疗效果，从而弥合临床前研究与临床应用之间的差距。尽管具有潜力，但circRNA在实体瘤CAR-T细胞疗法的临床应用中仍未得到充分探索，这为创新提供了重大机遇。circRNA调节CAR-T细胞耗竭、持久性和肿瘤特异性的机制尚未完全了解，并且仍需解决诸如实现高效且靶向的circRNA递送等技术挑战。本综述强调了将circRNA整合到CAR-T细胞疗法中以提高特异性、最小化脱靶效应并改善治疗持久性的重要性。通过强调circRNA的创新潜力并识别关键研究差距，本综述为推进CAR-T细胞疗法并为下一代个性化癌症治疗奠定基础提供了路线图。
