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基于 CAR 的细胞与基因治疗:来自 ClinicalTrials.gov 的全球临床格局与新兴治疗策略

英文原题:CAR-Based Cell and Gene Therapies: Global Clinical Landscape and Emerging Therapeutic Strategies from ClinicalTrials.gov.

PubMed 2025/10/27(内容时间) Biomol Ther (Seoul) Q1 · IF 4.9(JCR 2025)

研究概要

约 92% 的试验针对肿瘤,其中血液系统恶性肿瘤占 65% 的适应症;CD19 和 BCMA 是 III 期研究中的主要靶点。

中文摘要

基于嵌合抗原受体(CAR)的细胞和基因疗法已成为具有变革意义的治疗方法,可提供靶向且持久的应答,尤其适用于血液系统恶性肿瘤。本综述分析了截至2024年在ClinicalTrials.gov登记的1744项CAR临床试验,重点考察平台类型、适应证、靶抗原、治疗策略及后期开发情况。CAR-T疗法占主导,其次为CAR-NK、CAR-NKT、CAR-M和CAR-DC平台。约92%的试验以肿瘤为靶点,其中血液系统恶性肿瘤占适应证的65%;CD19和BCMA是III期研究中的主要靶点。实体瘤应用持续拓展,驱动因素包括未满足的临床需求及CAR工程化进展。尽管单特异性CAR仍占多数,但为克服抗原异质性和肿瘤逃逸,双靶点、双特异性及通用型设计日益受到关注。CAR-T联合化疗或单克隆抗体等联合治疗也越来越常见,以提高疗效。CAR-NK疗法虽仍处于早期开发阶段,但凭借较好的安全性特征和现货型异体应用潜力显示出前景。美国和中国依托强大的科研生态和产业投资引领全球开发。总体而言,CAR疗法正从专注血液肿瘤向更广泛的临床应用演变,并不断应对挑战、引导未来策略。

展开英文摘要原文

Chimeric Antigen Receptor (CAR)-based cell and gene therapies have become transformative treatments, offering targeted and durable responses, especially in hematologic malignancies. This review analyzes 1,744 CAR clinical trials registered on Clinical-Trials.gov as of 2024, focusing on platform types, indications, target antigens, therapeutic strategies, and late-phase development. CAR-T therapies predominate, followed by CAR-NK, CAR-NKT, CAR-M and CAR-DC platforms. Approximately 92% of trials target tumors, with hematologic malignancies accounting for 65% of indications; CD19 and BCMA are primary targets in Phase 3 studies. Solid tumor applications are expanding steadily, driven by unmet clinical needs and advances in CAR engineering. Although monospecific CARs dominate, dual, bispecific, and universal designs are gaining traction to overcome antigen heterogeneity and tumor escape. Combination therapies, such as CAR-T with chemotherapy or monoclonal antibodies, are increasingly used to improve efficacy. CAR-NK therapies, while in early development, show promise due to favorable safety profiles and off-the-shelf allogeneic potential. The United States and China lead global development, supported by robust research ecosystems and industrial investment. Overall, CAR-based therapeutics are evolving from hematologic specialization toward broader clinical application, addressing challenges and guiding future strategies.

论文信息

作者
Moon S、Song K
单位
College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea.South Korea
文献类型
综述
期刊
Biomolecules & therapeutics2025 Nov 1
原文标识
PubMed 41139478 · DOI 10.4062/biomolther.2025.153