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

作者：Gui Zhao, Yue Zhang, Cong‐Fei Xu, Jun Wang · 发表于：中国科学通报：英文版 · 年份：2023 · DOI：10.1016/j.scib.2023.11.055 · 被引用次数：55 · 研究领域：CAR-T cell therapy research、Virus-based gene therapy research、Nanowire Synthesis and Applications

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 (αCD19) CAR protein onto T-cells to produce αCD19 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 therapeutic membrane proteins.