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