Enhancing T cell therapy through TCR-signaling-responsive nanoparticle drug delivery.
Enhancing T cell therapy through TCR-signaling-responsive nanoparticle drug delivery.
复制标题
DOI：
10.1038/nbt.4181
复制
发表时间：
2018-09
影响因子：
46.9
通讯作者：
Irvine DJ
中科院分区：
文献类型：
--
作者：
Tang L;Zheng Y;Melo MB;Mabardi L;Castaño AP;Xie YQ;Li N;Kudchodkar SB;Wong HC;Jeng EK;Maus MV;Irvine DJ
Adoptive cell therapy (ACT) with antigen-specific T cells has shown remarkable clinical success, but 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 using protein nanogels (NGs) that selectively release these cargos in response to T cell receptor (TCR) activation. We design cell surface-conjugated NGs that respond to an increase in T cell surface reduction potential upon antigen recognition, limiting drug release to sites of antigen encounter such as the tumor microenvironment. Using NGs carrying an IL-15 superagonist complex, we demonstrate that relative to systemic administration of free cytokines, NG delivery selectively expands T cells 16-fold in tumors, and allows at least 8-fold higher doses of cytokine to be administered without toxicity. The improved therapeutic window enables substantially increased tumor clearance by murine T cell and human CAR-T cell therapy in vivo.
登录
查看更多内容
影响因子：
17.1
作者：
Fedorov VD;Themeli M;Sadelain M
通讯作者：
Sadelain M
影响因子：
30.5
作者：
Chang VT;Fernandes RA;Ganzinger KA;Lee SF;Siebold C;McColl J;Jönsson P;Palayret M;Harlos K;Coles CH;Jones EY;Lui Y;Huang E;Gilbert RJC;Klenerman D;Aricescu AR;Davis SJ
通讯作者：
Davis SJ
影响因子：
14
作者：
Au KM;Satterlee A;Min Y;Tian X;Kim YS;Caster JM;Zhang L;Zhang T;Huang L;Wang AZ
通讯作者：
Wang AZ
影响因子：
6.6
作者：
Lin, Xuzhu;Zheng, Wei;Shen, Pingping
通讯作者：
Shen, Pingping
对癌症或病毒的收养免疫疗法。
影响因子：
29.7
作者：
Maus MV;Fraietta JA;Levine BL;Kalos M;Zhao Y;June CH
通讯作者：
June CH