In vivo production of CAR-T cells using virus-mimetic fusogenic nanovesicles

Gui Zhao ¹Yue Zhang ¹Cong-Fei Xu ²Jun Wang³

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作者信息

1. 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
2. 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
3. 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;Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education,South China University of Technology,Guangzhou 510006,China
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Abstract

Engineered T cells expressing chimeric antigen receptor(CAR)exhibit high response rates in B-cell malig-nancy 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 mem-brane in vivo,thereby delivering the loaded anti-CD19(αCD19)CAR protein onto T-cells to produceαCD19 CAR-T cells.These αCD19 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 ther-apeutic membrane proteins.

Key words

CAR-T/Nanovesicle/Fusogen/Cancer immunotherapy

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基金项目

National Key R&D Program of China(2022YFB3808100)

National Natural Science Foundation of China(32271442)

National Natural Science Foundation of China(52130301)

National Natural Science Foundation of China(82072048)

Guangdong Basic and Applied Basic Research Foundation(2022B1515020025)

Science and Technology Program of Guangzhou,China(202103030004)

Fundamental Research Funds for the Central Universities(2022ZYGXZR102)

出版年

2024

科学通报(英文版)

中国科学院

科学通报(英文版)

CSTPCD

ISSN：1001-6538

参考文献量38

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