适体
封锁
免疫疗法
免疫检查点
癌症研究
T细胞
免疫系统
配体(生物化学)
化学
细胞
受体
细胞生物学
生物
分子生物学
免疫学
生物化学
作者
Yang Sun,Liuting Mo,Xiaoxiao Hu,Die Yu,Sitao Xie,Jianglin Li,Zilong Zhao,Xiaohong Fang,Mao Ye,Liping Qiu,Weihong Tan,Yu Yang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2022-12-09
卷期号:16 (12): 21129-21138
被引量:20
标识
DOI:10.1021/acsnano.2c09093
摘要
Cytotoxic T cells initiate antitumor effects mainly through direct interactions with tumor cells. As a counter to this, tumor cells can put the brakes on such T-cell activity via specific linkage between programmed death ligand 1 (PDL1) and its receptor programmed cell death protein 1 (PD1). Bispecific inhibitors that enabled synchronous blockade of PD1 and PDL1, thereby releasing the brakes on T-cell antitumor activity, should significantly improve the efficacy of immune checkpoint blockade (ICB) therapy. In this work, we identified a DNA aptamer, Ap3, that could specifically recognize PDL1 on tumor cells and competed with the binding of PD1. By integrating Ap3 with an anti-PD1 aptamer, the bispecific aptamer Ap3-7c was constructed, and it showed promise for improving the T-cell immune response. We further designed a dibenzocyclooctyne (DBCO)-labeled bispecific aptamer, D-Ap3-7c, allowing covalent conjugation of aptamers onto PD1 and PDL1 after specific cell recognition. Our in vivo studies showed that this recognition-then-conjugation strategy could induce a potent immunological effect against tumors. This work is expected to provide clues for antitumor immunotherapy.
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