Li Xuyang, Hu Dan
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA; Ludwig Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Lustgarten Dedicated Laboratory for Pancreatic Cancer Research and the Bloomberg~Kimmel Institute Cancer Genetics and Genomics Research Program, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Ann Romney Center for Neurologic Diseases, Harvard Medical School and Mass General Brigham, Boston, MA 02115, USA.
Trends Immunol. 2025 Feb;46(2):91-93. doi: 10.1016/j.it.2025.01.005. Epub 2025 Jan 28.
Lim and colleagues demonstrate that synNotch transcriptional circuits engineered into T cells can be used to precisely control location-specific expression of payloads responding to antigen triggers, thus locally inhibiting unwanted immunity or neuroinflammation. With no off-tumor toxicity or systemic immunosuppression upon elimination of mouse brain tumors, this approach can achieve better efficacy than anticipated.
林和同事们证明，工程改造到T细胞中的合成Notch转录回路可用于精确控制对抗原触发作出反应的有效载荷的位置特异性表达，从而局部抑制不必要的免疫或神经炎症。在消除小鼠脑肿瘤时没有肿瘤外毒性或全身免疫抑制，这种方法可以实现比预期更好的疗效。
