癌症免疫疗法
适体
抗原
结合
免疫疗法
贪婪
免疫系统
T细胞
癌细胞
化学
生物
计算生物学
细胞生物学
分子生物学
癌症研究
癌症
免疫学
遗传学
数学
数学分析
作者
Rui Tang,Yu-Hao Fu,Bo Gong,Yingying Fan,Hong‐Hui Wang,Yan Huang,Zhou Nie,Ping Wei
标识
DOI:10.1002/anie.202205902
摘要
Synthetically directing T-cells against tumors emerges as a promising strategy in immunotherapy, while it remains challenging to smartly engage T cells with tunable immune response. Herein, we report an intelligent molecular platform to engineer T-cell recognition for selective activation to potently kill cancer cells. To this end, we fabricated a hybrid conjugate that uses a click-type DNA-protein conjugation to equip the T cell-engaging antibody with two distinct programmable DNA nanoassemblies. By integrating multiple aptameric antigen-recognitions within a dynamic DNA circuit, we achieved combinatorial recognition of triple-antigens on cancer cells for selective T-cell activation after high-order logic operation. Moreover, by coupling a DNA nanostructure, we precisely defined the valence of the antigen-binding aptamers to tune avidity, realizing effective tumor elimination in vitro and in vivo. Together, we present a versatile and programmable strategy for synthetic immunotherapy.
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