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模块化 CAR:无需重新改造即可适配 T 细胞

英文原题:The Modular CAR: Adapting T Cells without Reengineering Them.

PubMed 2026/09/04(内容时间) Cancer Immunol Res Q1 · IF 7.9(JCR 2025)

研究概要

嵌合抗原受体(CAR)T细胞的治疗潜力长期以来一直受到工程化受体静态性质的限制;一旦制造完成,该细胞就固定针对单一抗原,无法应对实体瘤所特有的免疫逃逸和抗原异质性。

中文摘要

嵌合抗原受体(CAR)T 细胞的治疗潜力长期以来受到工程化受体静态特性的限制;一旦制造完成,该细胞即被锁定于单一抗原,无法应对实体瘤所特有的免疫逃逸和抗原异质性。尽管双特异性构建体和逻辑门控回路等解决方案已被提出,但每一种都在制造时向细胞产品中编码了额外的复杂性,且不具备输注后重编程的能力。在本期,Kuo 及其同事报告了一种根本不同的策略——meditope 赋能 CAR,即将一个小型、结构正交的肽对接界面嵌入 CAR 的胞外结构域,从而将固定的细胞产品转化为可编程平台,可通过给予模块化衔接分子对其进行重定向、选择性扩增或精确追踪。参见 Kuo 等人的相关文章,第 XX 页。

展开英文摘要原文

The therapeutic potential of chimeric antigen receptor (CAR) T cells has long been limited by the static nature of the engineered receptor; once manufactured, the cell is committed to a single antigen, unable to respond to the immune evasion and antigen heterogeneity that define solid tumors. Although solutions such as bispecific constructs and logic-gated circuits have been proposed, each encodes additional complexity into the cell product at the time of manufacture, with no capacity for post-infusion reprogramming. In this issue, Kuo and colleagues report a fundamentally different strategy-the meditope-enabled CAR-in which a small, structurally orthogonal peptide-docking interface is embedded into the extracellular domain of the CAR, converting a fixed cellular product into a programmable platform that can be redirected, selectively expanded, or precisely tracked by administering a modular adapter molecule. See related article by Kuo et al., p. XX.

论文信息

作者
Ang MJY、Luo Z、Mitchell MJ
单位
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania.United States
期刊
Cancer immunology research2026 Sep 4
原文标识
PubMed 42695598 · DOI 10.1158/2326-6066.CIR-26-0906