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yexuqing木蟲(chóng)之王 (文學(xué)泰斗)
太陽(yáng)系系主任
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[交流]
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 編程改造組織感應(yīng)T細(xì)胞直達(dá)大腦進(jìn)行治療 ▲ 作者:MILOS S. SIMIC, PAYAL B. WATCHMAKER et al. ▲鏈接: https://www.science.org/doi/10.1126/science.adl4237 ▲摘要: 為了設(shè)計(jì)能夠特異性靶向中樞神經(jīng)系統(tǒng)(CNS)的細(xì)胞,我們鑒定了細(xì)胞外中樞神經(jīng)系統(tǒng)特異性抗原,包括中樞神經(jīng)系統(tǒng)細(xì)胞外基質(zhì)的成分和在神經(jīng)元或膠質(zhì)細(xì)胞上表達(dá)的表面分子。 用于檢測(cè)這些抗原的合成Notch受體被用于編程改造T細(xì)胞,僅在大腦中誘導(dǎo)不同有效載荷的表達(dá)。誘導(dǎo)嵌合抗原受體表達(dá)的CNS靶向T細(xì)胞有效清除了原發(fā)性和繼發(fā)性腦腫瘤,而不損害腦外交叉反應(yīng)細(xì)胞。 此外,局部遞送免疫抑制細(xì)胞因子白介素—10的中樞神經(jīng)系統(tǒng)靶向細(xì)胞可改善小鼠神經(jīng)炎癥模型的癥狀。 ▲ 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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