CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
编程组织感知 T 细胞以向大脑递送治疗药物
英文原题：Programming tissue-sensing T cells that deliver therapies to the brain.
查看英文原题
Programming tissue-sensing T cells that deliver therapies to the brain.
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中文摘要
为了设计能够特异性靶向中枢神经系统（CNS）的细胞，我们鉴定了细胞外CNS特异性抗原，包括CNS细胞外基质的成分以及神经元或胶质细胞上表达的表面分子。利用工程化改造以检测这些抗原的合成Notch受体，我们编程T细胞使其仅在大脑中诱导多种效应分子的表达。靶向CNS的T细胞诱导嵌合抗原受体表达后，能有效清除原发性和继发性脑肿瘤，且不损伤大脑外的交叉反应细胞。相反，靶向CNS的细胞局部递送免疫抑制细胞因子白细胞介素-10可改善神经炎症小鼠模型的症状。组织感知细胞代表了一种以解剖学靶向方式应对多种疾病的策略。
展开英文摘要原文
To engineer cells that can specifically target the central nervous system (CNS), we identified extracellular CNS-specific antigens, including components of the CNS extracellular matrix and surface molecules expressed on neurons or glial cells. Synthetic Notch receptors engineered to detect these antigens were used to program T cells to induce the expression of diverse payloads only in the brain.
CNS-targeted T cells that induced chimeric antigen receptor expression efficiently cleared primary and secondary brain tumors without harming cross-reactive cells outside of the brain. Conversely, CNS-targeted cells that locally delivered the immunosuppressive cytokine interleukin-10 ameliorated symptoms in a mouse model of neuroinflammation. Tissue-sensing cells represent a strategy for addressing diverse disorders in an anatomically targeted manner.
论文信息
- 作者
- Simic MS、Watchmaker PB、Gupta S、Wang Y、Sagan SA、Duecker J、Shepherd C、Diebold D
- 单位
- UCSF Cell Design Institute and Department of Cellular & Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.United States
- 文献类型
- 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Science (New York, N.Y.)2024 Dec 6
- 原文标识
- PubMed 39636984 · DOI 10.1126/science.adl4237
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