免疫疗法
癌症研究
巨噬细胞
肿瘤微环境
转移
嵌合抗原受体
细胞
体内
癌症免疫疗法
适体
生物
体外
免疫学
癌症
免疫系统
分子生物学
生物化学
肿瘤细胞
生物技术
遗传学
作者
Husun Qian,Yixin Fu,Minkang Guo,Yu Chen,Dian Zhang,Yu Wei,Fangfang Jin,Qian Zeng,Yange Wang,Chee-Yin Chai,Shijia Ding,Wei Cheng,Tingmei Chen
标识
DOI:10.1016/j.ymthe.2022.04.015
摘要
Chimeric antigen receptor T (CAR-T) cell therapy has faced a series of challenges and has shown very little efficacy in solid tumors to date. Although genetically engineered macrophages have achieved definite therapeutic effect in solid tumors, heterogeneous expression of engineered proteins and the potential for toxicity limit further applications. Herein, we propose a nongenetic and simple macrophage cell engineering strategy through glycan metabolic labeling and click reaction for the treatment of solid tumors. The aptamer-engineered M1 macrophage (ApEn-M1) showed enhanced active targeting ability for tumor cells in vitro and in vivo, resulting in significant cytotoxicity effects. Moreover, ApEn-M1 exhibited superior antitumor efficacy in a breast cancer xenograft mouse model and a lung metastasis mouse model of breast cancer. Interestingly, the ApEn-M1 could reprogram the immunity microenvironment by increasing T cell infiltration and enhancing T cell activity in the tumor region. Additionally, the administration of ApEn-M1 showed no obvious systemic side effects. With glycan metabolic labeling, the macrophages could be efficiently labeled with aptamers on the cell surface via click reaction without genetic alteration or cell damage. Hence, this study serves as a proof of concept for cell-surface anchor engineering and expands the range of nongenetic macrophage cell engineering strategies.
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