肿瘤细胞治疗研究
英文原题：In vivo engineering of CAR immune cells by nonviral nanoparticles.
嵌合抗原受体（CAR）免疫细胞疗法已经彻底改变了血液系统恶性肿瘤的治疗，但传统的体外制造仍然成本高昂、工艺复杂且物流要求苛刻。
嵌合抗原受体（CAR）免疫细胞疗法已经彻底改变了血液系统恶性肿瘤的治疗，然而传统的体外制造仍然成本高昂、工艺复杂且物流要求苛刻。新兴的体内工程策略，尤其是基于非病毒纳米颗粒（NPs）的策略，通过实现体内直接编程免疫细胞，提供了一种变革性的替代方案。近年来，NPs介导的CAR构建体递送取得了进展，包括mRNA、环状RNA（circRNA）、自扩增RNA（saRNA）、DNA和基因编辑工具，已展现出实现瞬时、可调控且可重复表达并降低遗传毒性的良好潜力。针对T细胞、NK细胞和巨噬细胞的多种靶向策略已实现免疫细胞靶向，从而能够在疾病相关情境中精确控制CAR表达和功能激活。具体针对T细胞，按抗体类型分类的抗体功能化NPs包括CD3、CD4、CD5、CD7和CD8，显示出对T细胞亚群的不同结合，并在各种治疗情境中影响其激活特征。本综述重点介绍了免疫细胞靶向NPs开发中的关键进展，讨论了不断演变的CAR架构和质量控制考量，并概述了将体内CAR平台整合到更广泛免疫治疗格局中的未来方向。非病毒NPs有望通过实现可扩展、即用型免疫干预用于癌症、自身免疫性疾病和纤维化疾病，从而重新定义CAR治疗。
Chimeric antigen receptor (CAR) immune cell therapy has revolutionized the treatment of hematologic malignancies, yet conventional ex vivo manufacturing remains costly, complex, and logistically demanding. Emerging in vivo engineering strategies, especially those based on nonviral nanoparticles (NPs), offer a transformative alternative by enabling direct programming of immune cells within the body. Recent advances in NPs-mediated delivery of CAR constructs, including mRNA, circular RNA (circRNA), self-amplifying RNA (saRNA), DNA and gene editing tools, have demonstrated promising potential for achieving transient, tunable and repeatable expression with reduced genotoxicity. Immune cell targeting has been achieved by multiple targeting strategies for T cells, NK cells and macrophages, allowing precise control of CAR expression and functional activation in disease-relevant contexts. For T cells specifically, antibody-functionalized NPs categorized by antibody types including CD3, CD4, CD5, CD7 and CD8, demonstrate differential engagement of T cell subsets and influence their activation profiles across various therapeutic contexts. This review highlights key advances in the development of immune cell targeting NPs, discusses evolving CAR architectures and quality control considerations, and outlines future directions for integrating in vivo CAR platforms into broader immunotherapeutic landscapes. Nonviral NPs are poised to redefine CAR therapy by enabling scalable, off-the-shelf immune interventions for cancer, autoimmune, and fibrotic diseases.
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