文献类型：期刊文献

英文题名：Nano-Biohybrid DNA Engager That Reprograms the T-Cell Receptor

作者：Ma, Pei-Qiang[1];Liu, Tian-Xian[1];Li, Hua-Dong[1];Yin, Bin-Cheng[1,2];Ye, Bang-Ce[1,2,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Lab Biosyst & Microanal, Shanghai 200237, Peoples R China;[2]Zhejiang Univ Technol, Inst Engn Biol & Hlth, Coll Pharmaceut Sci, Collaborat Innovat Ctr Yangtze River Delta Reg Gre, Hangzhou 310014, Zhejiang, Peoples R China;[3]Shihezi Univ, Sch Chem & Chem Engn, Shihezi 832000, Xinjiang, Peoples R China

年份：2022

卷号：144

期号：49

起止页码：22458

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20225013226313);WOS:【SCI-EXPANDED(收录号:WOS:000891590800001)】；

基金：? ACKNOWLEDGMENTS This work was jointly supported by the National Key Research and Development Program of China (grant 2020YFA0908800) , National Natural Science Foundation of China (grants 21822402, 22134003, 31730004, and 22104037) , ?Shuguang Program? supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission (grant 20SG26) , and the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China (grant LHDMZ22H300008) .

语种：英文

外文关键词：Cell engineering - Cell membranes - Cell signaling - Chemical activation - Cytology - DNA - Genetic engineering

摘要：Although engineered T cells with transgenic chimeric antigen receptors (CARs) have made a breakthrough in cancer therapeutics, this approach still faces many challenges in the specificity, efficacy, and self-safety of genetic engineering. Here, we developed a nano-biohybrid DNA engager-reprogrammed T-cell receptor (EN-TCR) system to improve the specificity and efficacy, mitigate the excessive activation, and shield against risks from transgenesis, thus achieving a diversiform and precise control of the T-cell response. Utilizing modular assembly, the EN-TCR system can graft different specificities on T cells via antibody assembly. Besides, the designability of DNA hybridization enables precise target recognition by the library of multiantigen cell recognition circuits and allows gradual tuning of the T-cell activation level by the signaling switch and independent control over different types of T cells. Furthermore, we demonstrated the effectiveness of the system in tumor models. Together, this study provides a nongenetic T-cell engineering strategy to overcome major hindrances in T-cell therapy and may be extended to a general and convenient cell engineering strategy.