IL-12 nanochaperone-engineered CAR T cell for robust tumor-immunotherapy.
|
| Abstract |
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.
|
|---|---|
| Authors | Yingmei Luo, Ze Chen, Mingjian Sun, Baohong Li, Fan Pan, Aiqing Ma, Jianhong Liao, Ting Yin, Xiaofan Tang, Guojun Huang, Baozhen Zhang, Hong Pan, Mingbin Zheng, Lintao Cai |
| Journal | Biomaterials (Biomaterials) Vol. 281 Pg. 121341 (02 2022) ISSN: 1878-5905 [Electronic] Netherlands |
| PMID | 34995901 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2022 Elsevier Ltd. All rights reserved. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!