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概念 CAR 加速发展

英文原题:Concept CARs are picking up speed.

查看英文原题

Concept CARs are picking up speed.

PubMed 2025/05/08(内容时间) Mol Ther Q1 · IF 11.4(JCR 2025)

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中文摘要

过继T细胞免疫治疗领域长期以一种嵌合抗原受体(CAR)设计为主流:通过抗体来源结构域识别抗原,并将信号传导整合到单一多肽中。这种经典设计将T细胞强大的细胞毒潜能导向肿瘤,是多种商业化CAR-T 细胞产品的核心。该领域近期研究聚焦于开发更有效的CAR设计,尤其针对实体瘤。尽管大多数方法是在传统CAR设计基础上进行叠加改良,近期研究则回归基本设计,重新设计CAR,使其保留更多免疫受体(如T细胞受体或杀伤细胞免疫球蛋白样受体)的天然结构。与传统CAR设计相比,这些重新设计的CAR在临床前模型中表现出更强功能,在治疗难度更大的实体瘤模型中亦是如此;其中若干设计已进入临床研究,相关活性数据陆续出现。这些发现凸显了CAR设计的重要性,并提示开发新型T细胞免疫疗法时应超越传统CAR。

展开英文摘要原文

The field of adoptive T cell immunotherapy has been dominated by a chimeric antigen receptor (CAR) design that combines antigen recognition through antibody-derived domains and signaling into a single polypeptide. This conventional design redirects the immense cytotoxic potential of T cells toward tumors, and it is the core of several commercially marketed CAR-T cell products. Recent research in the field has been focused on developing more effective CAR designs, especially for solid tumors.

Although most approaches have layered on top of the conventional CAR design, recent studies have taken a step back and redesigned the basic CAR to retain more of the natural structure of immunoreceptors such as the T cell receptor or killer immunoglobulin-like receptors.

These redesigned CARs promote enhanced function in preclinical models compared with conventional CAR designs, including in the more challenging solid tumor setting, and several have entered the clinic with emerging data on their activity. These observations highlight the importance of considering CAR design and looking beyond conventional CARs when developing new T cell immunotherapy approaches.

论文信息

作者
Mansilla-Soto J、Milone MC
第一作者单位
Departments of Immunology, Bioengineering, and BMT and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.United States
通讯作者单位
Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: milone@pennmedicine.upenn.edu.United States
文献类型
综述
期刊
Molecular therapy : the journal of the American Society of Gene Therapy2025 Jun 4
原文标识
PubMed 40340247 · DOI 10.1016/j.ymthe.2025.05.008