CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
DROP-CARs：用临床获批小分子工程化可逆、药物控制的 CAR-T 细胞活性
英文原题：DROP-CARs: Engineering Reversible, Drug-Controlled CAR T-cell Activity with a Clinically Approved Small Molecule.
查看英文原题
DROP-CARs: Engineering Reversible, Drug-Controlled CAR T-cell Activity with a Clinically Approved Small Molecule.
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中文摘要
将嵌合抗原受体（CAR）T细胞应用于实体瘤的一个主要限制是，由于缺乏肿瘤特异性靶点，健康组织会产生毒性。克服这种有害细胞毒性的一种有前景的策略是，在CAR-T 细胞中引入除抗原识别之外的控制机制。在最近一期《Nature Chemical Biology》中，Scheller及其同事报告了一种CAR的开发，该CAR通过引入小分子venetoclax而失活，venetoclax是一种临床上已批准的靶向Bcl-2抑制剂。作者设计了venetoclax依赖性的CAR胞外结合域释放，从而破坏T细胞与肿瘤细胞的接触并抑制细胞毒性。此外，他们证明了该方法的可逆性，因为撤除药物后可恢复CAR-T 细胞功能。这项工作为用于实体瘤、可临床转化的遥控CAR-T 细胞疗法奠定了基础。
展开英文摘要原文
A major limitation in applying chimeric antigen receptor (CAR) T cells to solid tumors is toxicity in healthy tissues caused by a lack of tumor-specific targets. A promising strategy to overcome this deleterious cytotoxicity is to engineer control into CAR T cells beyond that conferred by antigen recognition alone.
In a recent issue of Nature Chemical Biology, Scheller and colleagues report the development of a CAR that is inactivated through introducing the small molecule, venetoclax, which is a clinically approved targeted Bcl-2 inhibitor. The authors design venetoclax-dependent release of the CAR extracellular binding domain, thereby disrupting T-cell contact with tumor cells and suppressing cytotoxicity.
Furthermore, they demonstrate the reversibility of this approach as withdrawal of the drug restores CAR T-cell function. This work establishes a foundation for clinically translatable remote-controlled CAR T-cell therapy for solid tumors.
论文信息
- 作者
- Stevens AJ、Lim WA
- 第一作者单位
- Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.United States
- 通讯作者单位
- UCSF Cell Design Institute, University of California, San Francisco, California.United States
- 期刊
- Cancer research2026 Jul 15
- 原文标识
- PubMed 41941729 · DOI 10.1158/0008-5472.CAN-26-1348