体内嵌合抗原受体T细胞(in vivo CAR-T)研究进展及非临床研究一般考虑

doi:10.2095-3593.2025.120001

摘要/Abstract

摘要： 体外嵌合抗原受体T细胞(ex vivo CAR-T)在改善血液系统恶性肿瘤（尤其是B细胞恶性肿瘤）方面显示出卓越的治疗潜力，但其广泛应用面临巨大挑战，包括体外制造工艺复杂、生产成本高昂等因素。近年来，随着RNA药物、靶向递送系统等领域的快速发展，体内嵌合抗原受体T细胞(in vivo CAR-T)作为一种创新策略应运而生。in vivo CAR-T通过病毒载体或脂质纳米颗粒（LNPs）等靶向递送系统，将编码CAR的遗传物质直接导入患者体内，实现体内T细胞工程化改造，这一策略从根本上省去了繁琐的体外细胞操作步骤和传统的化疗预处理环节。本研究系统梳理了in vivo CAR-T的技术进展与非临床研究考虑。in vivo CAR-T兼具基因治疗与细胞治疗的双重属性，涉及多种递送载体，类型多样，机制复杂，其非临床研究可遵循基于风险、个案处理的原则，在现有相关技术指导原则框架下，合理设计并开展非临床研究，以获取科学规范的试验数据来支持开展临床试验和批准上市。

关键词: font-size:medium, ">体内嵌合抗原受体T细胞（in vivo CAR-T）；非临床研究；病毒载体；LNP载体

Abstract: Chimeric antigen receptor (CAR)-T cell therapy has demonstrated significant therapeutic potential in hematologic malignancies (particularly B-cell malignancies). However， its broad application faces considerable challenges， including complex ex vivo manufacturing processes and high production costs. In recent years， with rapid advancements in RNA therapeutics and targeted delivery systems， in vivo generation of chimeric antigen receptor T cells (in vivo CAR-T) has emerged as an innovative strategy. This approach utilizes viral vectors or lipid nanoparticles (LNPs) as targeted delivery systems to directly introduce genetic material encoding the CAR into patients， enabling in vivo T cell engineering. This strategy fundamentally eliminates the need for cumbersome ex vivo cell manipulation steps and traditional chemotherapy-based preconditioning regimens. This article systematically reviews the technological progress and nonclinical research considerations for in vivo CAR-T. As in vivo CAR-T combines attributes of both gene therapy and cell therapy， involves diverse delivery vectors， and exhibits varied types and complex mechanisms， its nonclinical studies can be guided by risk-based， case-by-case principles. Within the framework of existing relevant technical guidelines， scientifically sound nonclinical studies should be rationally designed and conducted to generate robust experimental data supporting clinical trials and marketing approval.

Key words: font-size:medium, ">In vivo CAR-T； Non-clinical research； Viral vector； LNP vector

中图分类号:

周宇, 张旻, 闫莉萍. 体内嵌合抗原受体T细胞(in vivo CAR-T)研究进展及非临床研究一般考虑[J]. 中国药物评价, 2025, 42(6): 409-409-415.

ZHOU Yu, ZHANG Min, YAN Liping. Research Progress and General considerations on Nonclinical Evaluation of In Vivo Chimeric Antigen Receptor (CAR)-T Cell Therapy[J]. CHINESE JOURNAL OF DRUG EVALUATION, 2025, 42(6): 409-409-415.

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