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
限制 CAR-T 细胞迁移扩大可靶向抗原空间
英文原题：Restricting CAR T Cell Trafficking Expands Targetable Antigen Space.
查看英文原题
Restricting CAR T Cell Trafficking Expands Targetable Antigen Space.
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中文摘要
嵌合抗原受体（CAR）T细胞是某些血液癌症的有效治疗方法。然而，缺乏肿瘤特异性表面抗原限制了其更广泛的应用。我们鉴定了一组表面抗原，其表达仅限于癌症和中枢神经系统（CNS）。我们针对其中一种抗原LINGO1开发了CAR-T 细胞，该抗原在尤文肉瘤（ES）中广泛表达。为防止靶向CNS，我们工程化改造了缺乏整合素4（A4 ko）的LINGO1 CAR-T 细胞，整合素4是跨越血脑屏障迁移所必需的黏附分子。A4 ko LINGO1 CAR-T 细胞被有效排除在CNS之外，但保留了对ES的疗效。我们表明，改变黏附行为扩展了CAR-T 细胞可靶向的表面抗原集合。
展开英文摘要原文
Chimeric antigen receptor (CAR) T cells are an effective treatment for some blood cancers.
However, the lack of tumor-specific surface antigens limits their wider use.
We identified a set of surface antigens that are limited in their expression to cancer and the central nervous system (CNS).
We developed CAR T cells against one of these antigens, LINGO1, which is widely expressed in Ewing sarcoma (ES). To prevent CNS targeting, we engineered LINGO1 CAR T cells lacking integrin 4 (A4 ko ), an adhesion molecule essential for migration across the blood-brain barrier. A4 ko LINGO1 CAR T cells were efficiently excluded from the CNS but retained efficacy against ES.
We show that altering adhesion behavior expands the set of surface antigens targetable by CAR T cells.
论文信息
- 作者
- Morales EA、Dietze KA、Baker JM、Wang A、Avila SV、Iglesias F、Radhakrishnan SV、Mause EV
- 第一作者单位
- Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.United States
- 通讯作者单位
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.United States
- 文献类型
- 预印本
- 期刊
- bioRxiv : the preprint server for biology2024 Feb 11
- 原文标识
- PubMed 38370665 · DOI 10.1101/2024.02.08.579002