Meng Sikun, Hara Tomoaki, Miura Yutaka, Arao Yasuko, Saito Yoshiko, Inoue Kana, Hirotsu Takaaki, Vecchione Andrea, Satoh Taroh, Ishii Hideshi
Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
Laboratory for Chemistry and Life Science, Institute of Integrated Research, Institute of Science Tokyo, 4259 Nagatsutacho, Midori-ku, Yokohama 226-8501, Japan.
Int J Mol Sci. 2025 Mar 28;26(7):3119. doi: 10.3390/ijms26073119.
Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized cancer immunotherapy but continues to face significant challenges that limit its broader application, such as antigen targeting, the tumor microenvironment, and cell persistence, especially in solid tumors. Meanwhile, the global implementation of mRNA vaccines during the COVID-19 pandemic has highlighted the transformative potential of mRNA and lipid nanoparticle (LNP) technologies. These innovations, characterized by their swift development timelines, precise antigen design, and efficient delivery mechanisms, provide a promising framework to address some limitations of CAR-T therapy. Recent advancements, including mRNA-based CAR engineering and optimized LNP delivery, have demonstrated the capacity to enhance CAR-T efficacy, particularly in the context of solid tumors. This review explores how mRNA-LNP technology can drive the development of in vivo engineered CAR-T therapies to address current limitations and discusses future directions, including advancements in mRNA design, LNP optimization, and strategies for improving in vivo CAR-T functionality and safety. By bridging these technological insights, CAR-T therapy may evolve into a versatile and accessible treatment paradigm across diverse oncological landscapes.
嵌合抗原受体T细胞（CAR-T）疗法彻底改变了癌症免疫疗法，但仍面临着一些重大挑战，这些挑战限制了其更广泛的应用，如抗原靶向、肿瘤微环境和细胞持久性，尤其是在实体瘤中。与此同时，新冠疫情期间mRNA疫苗在全球的应用凸显了mRNA和脂质纳米颗粒（LNP）技术的变革潜力。这些创新具有快速的研发周期、精确的抗原设计和高效的递送机制，为解决CAR-T疗法的一些局限性提供了一个有前景的框架。最近的进展，包括基于mRNA的CAR工程和优化的LNP递送，已证明有能力提高CAR-T疗效，特别是在实体瘤方面。本综述探讨了mRNA-LNP技术如何推动体内工程化CAR-T疗法的发展以解决当前的局限性，并讨论了未来的方向，包括mRNA设计的进展、LNP优化以及改善体内CAR-T功能和安全性的策略。通过整合这些技术见解，CAR-T疗法可能会演变成一种适用于各种肿瘤情况的通用且可及的治疗模式。
