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In vivo production of CAR-T cells using virus-mimetic fusogenic nanovesicles.
- Source :
-
Science Bulletin . Feb2024, Vol. 69 Issue 3, p354-366. 13p. - Publication Year :
- 2024
-
Abstract
- [Display omitted] 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20959273
- Volume :
- 69
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Science Bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 174915276
- Full Text :
- https://doi.org/10.1016/j.scib.2023.11.055