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
高性能多重药物门控 CAR 线路
英文原题：High-performance multiplex drug-gated CAR circuits.
查看英文原题
High-performance multiplex drug-gated CAR circuits.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
嵌合抗原受体（CAR）T细胞可能彻底改变癌症医学。然而，过度激活、缺乏肿瘤特异性表面标志物以及抗原逃逸阻碍了CAR-T 细胞的发展。需要一种由临床批准药物调控的多抗原靶向CAR系统。在此，我们提出VIPER CAR（多功能蛋白酶可调控CAR），这是一组用病毒蛋白酶结构域工程化改造的可诱导ON和OFF开关CAR回路。我们在异种移植肿瘤和细胞因子释放综合征小鼠模型中，使用FDA批准的抗病毒蛋白酶抑制剂确立了其可控性。此外，我们将VIPER CAR与其他药物门控系统进行了基准比较，并展示了同类最佳的性能。我们使用ON VIPER CAR和OFF来那度胺-CAR系统在体内展示了它们的正交性。最后，我们通过结合各种CAR技术工程化改造了多种VIPER CAR回路。我们的多重、药物门控CAR回路代表了CAR设计的下一步进展，能够实现高级逻辑和调控，以增强CAR-T 细胞疗法的安全性。
展开英文摘要原文
Chimeric antigen receptor (CAR) T cells can revolutionize cancer medicine.
However, overactivation, lack of tumor-specific surface markers, and antigen escape have hampered CAR T cell development. A multi-antigen targeting CAR system regulated by clinically approved pharmaceutical agents is needed.
Here, we present VIPER CARs (versatile protease regulatable CARs), a collection of inducible ON and OFF switch CAR circuits engineered with a viral protease domain.
We established their controllability using FDA-approved antiviral protease inhibitors in a xenograft tumor and a cytokine release syndrome mouse model.
Furthermore, we benchmarked VIPER CARs against other drug-gated systems and demonstrated best-in-class performance.
We showed their orthogonality in vivo using the ON VIPER CAR and OFF lenalidomide-CAR systems.
Finally, we engineered several VIPER CAR circuits by combining various CAR technologies.
Our multiplexed, drug-gated CAR circuits represent the next progression in CAR design capable of advanced logic and regulation for enhancing the safety of CAR T cell therapy.
论文信息
- 作者
- Li HS、Wong NM、Tague E、Ngo JT、Khalil AS、Wong WW
- 第一作者单位
- Department of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA, USA.United States
- 通讯作者单位
- Department of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA, USA. Electronic address: wilwong@bu.edu.United States
- 文献类型
- 美国 NIH 资助研究 · 非美国政府资助研究 · 美国政府（非公共卫生署）资助研究
- 期刊
- Cancer cell2022 Nov 14
- 原文标识
- PubMed 36084652 · DOI 10.1016/j.ccell.2022.08.008
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →