摘要
Engineered T cells expressing chimeric antigen receptor(CAR)exhibit high response rates in B-cell malignancy treatments and possess therapeutic potentials against various diseases.However,the complicated ex vivo production process of CAR-T cells limits their application.Herein,we use virus-mimetic fusogenic nanovesicles(FuNVs)to produce CAR-T cells in vivo via membrane fusion-mediated CAR protein delivery.Briefly,the FuNVs are modified using T-cell fusogen,adapted from measles virus or reovirus fusogens via displaying anti-CD3 single-chain variable fragment.The FuNVs can efficiently fuse with the T-cell membrane in vivo,thereby delivering the loaded anti-CD19(aCD19)CAR protein onto T-cells to produce aCD19 CAR-T cells.These aCD19 CAR-T cells alone or in combination with anti-OX40 antibodies can treat B-cell lymphoma without inducing cytokine release syndrome.Thus,our strategy provides a novel method for engineering T cells into CAR-T cells in vivo and can further be employed to deliver other therapeutic membrane proteins.
作者
赵贵
张玥
许从飞
王均
Gui Zhao;Yue Zhang;Cong-Fei Xu;Jun Wang(School of Biomedical Sciences and Engineering,South China University of Technology,Guangzhou International Campus,Guangzhou 511442,China;National Engineering Research Center for Tissue Restoration and Reconstruction,South China University of Technology,Guangzhou 510006,China;Guangdong Provincial Key Laboratory of Biomedical Engineering,South China University of Technology,Guangzhou 510006,China;Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education,South China University of Technology,Guangzhou 510006,China)
基金
This work was supported by the National Key R&D Program of China(2022YFB3808100)
the National Natural Science Foundation of China(32271442,52130301,and 82072048)
the Guangdong Basic and Applied Basic Research Foundation(2022B1515020025)
the Science and Technology Program of Guangzhou,China(202103030004)
the Fundamental Research Funds for the Central Universities(2022ZYGXZR102).
作者简介
contributed equally:Gui Zhao received his master’s degree from University of Science and Technology of China in 2019,and subsequently received his Ph.D.degree from South China University of Technology in 2023.His research is primarily centered on nanomedicine-based approaches to regulate the immune system for the treatment of tumor and autoimmune diseases;contributed equally:Yue Zhang earned her master’s degree from University of Science and Technology of China in 2019,and then received her Ph.D.degree from South China University of Technology in 2023.Her research focuses on nanocarrier-based delivery of nucleic acid and protein drugs to enhance immunotherapy;Corresponding authors:Cong-Fei Xu serves as an associate professor at South China University of Technology.He earned his Ph.D.degree from the University of Science and Technology of China and subsequently completed a postdoctoral fellowship at South China University of Technology.His research is primarily focused on developing biomaterials and drug delivery systems for in vivo cell engineering applications,as well as utilizing nanomedicines to treat tumors,genetic diseases,and immune-related disorders.E-mail addresses:xucf@scut.edu.cn;Corresponding authors:Jun Wang is a professor at South China University of Technology.He earned his Ph.D.degree from Wuhan University and completed postdoctoral training at both Johns Hopkins in Singapore and the Johns Hopkins University School of Medicine.He served as a professor at the University of Science and Technology of China from 2004 to 2016.His research interests encompass biomedical materials,drug delivery,gene editing,and cancer immunotherapy.E-mail addresses:mcjwang@scut.edu.cn。
