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yexuqing木虫之王 (文学泰斗)
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Programming tissue-sensing T cells that deliver therapies to the brain
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Programming tissue-sensing T cells that deliver therapies to the brain 编程改造组织感应T细胞直达大脑进行治疗 ▲ 作者：MILOS S. SIMIC, PAYAL B. WATCHMAKER et al. ▲链接： https://www.science.org/doi/10.1126/science.adl4237 ▲摘要： 为了设计能够特异性靶向中枢神经系统（CNS）的细胞，我们鉴定了细胞外中枢神经系统特异性抗原，包括中枢神经系统细胞外基质的成分和在神经元或胶质细胞上表达的表面分子。 用于检测这些抗原的合成Notch受体被用于编程改造T细胞，仅在大脑中诱导不同有效载荷的表达。诱导嵌合抗原受体表达的CNS靶向T细胞有效清除了原发性和继发性脑肿瘤，而不损害脑外交叉反应细胞。 此外，局部递送免疫抑制细胞因子白介素—10的中枢神经系统靶向细胞可改善小鼠神经炎症模型的症状。 ▲ Abstract： 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. |
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