细胞因子
免疫系统
癌症研究
过继性细胞移植
细胞
细胞疗法
抗原
T细胞
医学
免疫学
化学
生物化学
作者
Yutong Liu,Kwasi Adu‐Berchie,Joshua M. Brockman,Matthew J. Pezone,David Zhang,Jingyi Zhou,Jason W. Pyrdol,Hua Wang,Kai W. Wucherpfennig,David J. Mooney
标识
DOI:10.1073/pnas.2213222120
摘要
Adoptive T cell transfer (ACT) therapies suffer from a number of limitations (e.g., poor control of solid tumors), and while combining ACT with cytokine therapy can enhance effectiveness, this also results in significant side effects. Here, we describe a nanotechnology approach to improve the efficacy of ACT therapies by metabolically labeling T cells with unnatural sugar nanoparticles, allowing direct conjugation of antitumor cytokines onto the T cell surface during the manufacturing process. This allows local, concentrated activity of otherwise toxic cytokines. This approach increases T cell infiltration into solid tumors, activates the host immune system toward a Type 1 response, encourages antigen spreading, and improves control of aggressive solid tumors and achieves complete blood cancer regression with otherwise noncurative doses of CAR-T cells. Overall, this method provides an effective and easily integrated approach to the current ACT manufacturing process to increase efficacy in various settings.
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