机构：[1]Laboratory of Human Diseases and Immunotherapy, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[2]Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[3]Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院[4]Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China.四川大学华西医院
Traditional antibody-drug conjugates (ADCs) mainly suppress tumor growth through either chemotherapy with cytotoxic payloads or immunotherapy with immuno-modulators. However, a single therapeutic modality may limit their exploration. Herein, we developed a new type of drug conjugate termed CAR-EDC (CAR-M-derived exosome-drug conjugate) by using CAR-exosomes from CAR-M cells as the targeting drug carrier that contains a high level of CXCL10. CAR-exosomes could significantly enhance the immunological activation and migratory capacity of T lymphocytes and promote their differentiation into CD8+ T cells. It also increased the proportion of M1 macrophages. The CAR-EDC, covalently loaded with SN-38, was internalized into Raji cells through endocytosis mediated by the CAR molecules. It exerted excellent antitumor activity in vivo by virtue of not only chemotherapy by SN38 but also immunotherapy by CXCL10-mediated antitumor immunity. Generally, this study provides an exosome-drug conjugate system with enhanced antitumor effects over traditional ADCs through the synergism of chemotherapy and immunotherapy.
基金：
This work was financially supported by grants from the
National Natural Science Foundation of China (21977076 and
82100354) and Science & Technology Department of Sichuan
Province (23NSFSC4548, 23NSFSC0012 and 23SYSX0082).
We thank Dr. Congmei Cao and Dr. Yu Chen (HitGen Inc.,
Chengdu, China) for mass spectrometry analysis.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2024]版：
无
最新[2023]版：
大类|1 区医学
小类|1 区药物化学
第一作者：
第一作者机构：[1]Laboratory of Human Diseases and Immunotherapy, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.[2]Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.[3]Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.[4]Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China.
共同第一作者：
通讯作者：
通讯机构：[1]Laboratory of Human Diseases and Immunotherapy, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.[2]Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.[3]Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.[4]Cardiovascular Surgery Research Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China.
推荐引用方式(GB/T 7714)：
Jiang Yunhan,Xu Xiaoqiu,Fan Dongmei,et al.Advancing Tumor-Targeted Chemo-Immunotherapy: Development of the CAR-M-derived Exosome-Drug Conjugate[J].Journal Of Medicinal Chemistry.2024,doi:10.1021/acs.jmedchem.4c00753.
APA：
Jiang Yunhan,Xu Xiaoqiu,Fan Dongmei,Liu Pingxian,Zhou Meng...&Yang Tao.(2024).Advancing Tumor-Targeted Chemo-Immunotherapy: Development of the CAR-M-derived Exosome-Drug Conjugate.Journal Of Medicinal Chemistry,,
MLA：
Jiang Yunhan,et al."Advancing Tumor-Targeted Chemo-Immunotherapy: Development of the CAR-M-derived Exosome-Drug Conjugate".Journal Of Medicinal Chemistry .(2024)
医学