1. Academic Validation
  2. IL-12 nanochaperone-engineered CAR T cell for robust tumor-immunotherapy

IL-12 nanochaperone-engineered CAR T cell for robust tumor-immunotherapy

  • Biomaterials. 2022 Feb;281:121341. doi: 10.1016/j.biomaterials.2021.121341.
Yingmei Luo 1 Ze Chen 2 Mingjian Sun 3 Baohong Li 4 Fan Pan 2 Aiqing Ma 4 Jianhong Liao 2 Ting Yin 4 Xiaofan Tang 2 Guojun Huang 2 Baozhen Zhang 2 Hong Pan 5 Mingbin Zheng 6 Lintao Cai 7
Affiliations

Affiliations

  • 1 Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, PR China; Key Laboratory for Nanomedicine, Department of Histology and Embryology and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, PR China.
  • 2 Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, PR China.
  • 3 School of Information Science and Engineering, Harbin Institute of Technology, Weihai, Shandong, 264209, China.
  • 4 Key Laboratory for Nanomedicine, Department of Histology and Embryology and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, PR China.
  • 5 Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, PR China. Electronic address: hong.pan@siat.ac.cn.
  • 6 Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, PR China; National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Southern University of Science and Technology Shenzhen, 518112, PR China; Key Laboratory for Nanomedicine, Department of Histology and Embryology and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, PR China; Zhuhai Institute of Advanced Technology Chinese Academy of Sciences, 519000, Zhuhai, PR China. Electronic address: mb.zheng@siat.ac.cn.
  • 7 Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, CAS-HK Joint Lab of Biomaterials, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, PR China; Zhuhai Institute of Advanced Technology Chinese Academy of Sciences, 519000, Zhuhai, PR China. Electronic address: lt.cai@siat.ac.cn.
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.

Keywords

CAR T cell therapy; Immunofeedback pathway; Immunosuppression; Interleukin 12; Nanochaperone.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-136976
    ≥98.0%, Cell Proliferation Assay Reagent