嵌合抗原受体
T细胞
癌症研究
免疫疗法
免疫系统
肿瘤微环境
抗原
免疫学
医学
作者
Yingmei Luo,Ze Chen,Mingjian Sun,Baohong Li,Fan Pan,Ai-Qing Ma,Jian‐Hong Liao,Ting Yin,Xiaofan Tang,Guojun Huang,Baozhen Zhang,Hong Pan,Mingbin Zheng,Lintao Cai
出处
期刊:Biomaterials
[Elsevier]
日期:2022-02-01
卷期号:281: 121341-121341
被引量:58
标识
DOI:10.1016/j.biomaterials.2021.121341
摘要
Although chimeric antigen receptor T (CAR T) cell immunotherapy has demonstrated remarkable success in clinical, therapeutic effects are still limited in solid tumor due to lack of activated T cell infiltration in immunosuppression of tumor microenvironment. Herein, we develop IL-12 nanostimulant-engineered CAR T cell (INS-CAR T) biohybrids for boosting antitumor immunity of CAR T cells via immunofeedback. As stimulating nanochaperone, IL-12-loaded human serum albumin (HSA) nanoparticles are effectively conjugated onto CAR T cells via bioorthogonal chemistry without influencing their antitumor capabilities. IL-12 is responsively released from INS-CAR T biohybrids in presence of the increased thiol groups on cell-surface triggered by tumor antigens. In return, released IL-12 obviously promotes the secretion of CCL5, CCL2 and CXCL10, which further selectively recruits and expands CD8+ CAR T cells in tumors. Ultimately, the immune-enhancing effects of IL-12 nanochaperone significantly boost CAR T cell antitumor capabilities, dramatically eliminated solid tumor and minimized unwanted side effects. Hence, immunofeedback INS-CAR T biohybrids, which include INS that serves as an intelligent ‘nanochaperone’, could provide a powerful tool for efficient and safe antitumor immunotherapy.
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