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
CD99 介导的免疫突触形成增强 CAR-T 细胞功能
英文原题：CD99-mediated immunological synapse formation potentiates CAR-T cell function.
查看英文原题
CD99-mediated immunological synapse formation potentiates CAR-T cell function.
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
尽管嵌合抗原受体（CAR）-T细胞在选定的血液系统恶性肿瘤中具有疗效，但仍需要进一步改进CAR-T 的设计。我们假设，通过修饰CAR结构以增强免疫突触（IS）稳定性和CAR靶标结合可能是一种可行的策略。在这里，我们表明膜蛋白CD99通过介导肌动蛋白-微管相互作用对T细胞中IS的形成至关重要。CD99缺失会消除IS形成并阻止有效的体内T细胞免疫。机制上，CD99分别通过跨膜结构域和胞质结构域与微管和肌动蛋白相互作用，肌球蛋白和IQGAP1与之相互作用。因此，将CD99的跨膜和近膜结构域整合到CAR结构中可增强IS形成，并提高人CAR-T 细胞在免疫缺陷小鼠中对抗淋巴瘤的治疗效果。因此，我们的数据表明，CD99介导的IS稳定可能有助于改善CAR设计和疗效。
展开英文摘要原文
Despite the efficacy of chimeric antigen receptor (CAR)-T cells in selected hematological malignancies, further improvement on CAR-T designs is still desirable.
We hypothesize that modifying the CAR structure to enhance immunological synapse (IS) stabilization and CAR target-binding may be a feasible strategy.
Here we show that the membrane protein, CD99, is critical for IS formation in T cells by mediating actin-microtubule interaction. CD99 deficiency abolishes IS formation and prevents effective in vivo T cell immunity.
Mechanistically, CD99 interacts with microtubules and actins through the transmembrane and cytoplasmic domains, respectively, with which myosin and IQGAP1 interact. As such, incorporating the transmembrane and juxtamembrane domains of CD99 into the CAR structure enhances IS formation and improves the therapeutic efficacy of human CAR-T cells against lymphoma in immune-deficient mice.
Our data thus suggest that CD99-mediated IS stabilization may help improve CAR design and efficacy.
论文信息
- 作者
- Nam G、Yeon HR、Park HB、Chang H、Kim JH、Cho BK、Jung H、Yi EC
- 第一作者单位
- Department of Biomedical Sciences, Seoul National University, Seoul, 03080, Republic of Korea.South Korea
- 通讯作者单位
- Department of Biomedical Sciences, Seoul National University, Seoul, 03080, Republic of Korea. eycii@snu.ac.kr.South Korea
- 期刊
- Nature communications2025 Aug 27
- 原文标识
- PubMed 40866332 · DOI 10.1038/s41467-025-63184-w
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 →