作者
Li Tang, Yiran Zheng, Mariane Bandeira Melo, Llian Mabardi, Ana P Castaño, Yu-Qing Xie, Na Li, Sagar B Kudchodkar, Hing C Wong, Emily K Jeng, Marcela V Maus, Darrell J Irvine
发表日期
2018/9
期刊
Nature biotechnology
卷号
36
期号
8
页码范围
707-716
出版商
Nature Publishing Group US
简介
Adoptive cell therapy (ACT) with antigen-specific T cells has shown remarkable clinical success; however, approaches to safely and effectively augment T cell function, especially in solid tumors, remain of great interest. Here we describe a strategy to 'backpack' large quantities of supporting protein drugs on T cells by using protein nanogels (NGs) that selectively release these cargos in response to T cell receptor activation. We designed cell surface–conjugated NGs that responded to an increase in T cell surface reduction potential after antigen recognition and limited drug release to sites of antigen encounter, such as the tumor microenvironment. By using NGs that carried an interleukin-15 super-agonist complex, we demonstrated that, relative to systemic administration of free cytokines, NG delivery selectively expanded T cells 16-fold in tumors and allowed at least eightfold higher doses of cytokine to be …
学术搜索中的文章
L Tang, Y Zheng, MB Melo, L Mabardi, AP Castaño… - Nature biotechnology, 2018