A lentiviral vector for the production of T cells with an inducible transgene and a constitutively expressed tumour-targeting receptor.

Details

Ressource 1Download: 37069267_BIB_22CADB5FE4EC.pdf (5572.66 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_22CADB5FE4EC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A lentiviral vector for the production of T cells with an inducible transgene and a constitutively expressed tumour-targeting receptor.
Journal
Nature biomedical engineering
Author(s)
Reichenbach P., Giordano Attianese GMP, Ouchen K., Cribioli E., Triboulet M., Ash S., Saillard M., Vuillefroy de Silly R., Coukos G., Irving M.
ISSN
2157-846X (Electronic)
ISSN-L
2157-846X
Publication state
Published
Issued date
09/2023
Peer-reviewed
Oui
Volume
7
Number
9
Pages
1063-1080
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Vectors that facilitate the engineering of T cells that can better harness endogenous immunity and overcome suppressive barriers in the tumour microenvironment would help improve the safety and efficacy of T-cell therapies for more patients. Here we report the design, production and applicability, in T-cell engineering, of a lentiviral vector leveraging an antisense configuration and comprising a promoter driving the constitutive expression of a tumour-directed receptor and a second promoter enabling the efficient activation-inducible expression of a genetic payload. The vector allows for the delivery of a variety of genes to human T cells, as we show for interleukin-2 and a microRNA-based short hairpin RNA for the knockdown of the gene coding for haematopoietic progenitor kinase 1, a negative regulator of T-cell-receptor signalling. We also show that a gene encoded under an activation-inducible promoter is specifically expressed by tumour-redirected T cells on encountering a target antigen in the tumour microenvironment. The single two-gene-encoding vector can be produced at high titres under an optimized protocol adaptable to good manufacturing practices.
Keywords
Humans, Lentivirus/genetics, T-Lymphocytes, Transgenes/genetics, Promoter Regions, Genetic/genetics, Neoplasms/genetics, Neoplasms/therapy, Tumor Microenvironment
Pubmed
Web of science
Open Access
Yes
Create date
25/04/2023 13:14
Last modification date
23/01/2024 7:21
Usage data