Gene editing enables T-cell engineering to redirect antigen specificity for potent tumor rejection.
Animals
CRISPR-Associated Protein 9
/ genetics
Cell Engineering
/ methods
Cell Line
Gene Editing
/ methods
Genes, T-Cell Receptor alpha
/ genetics
Genetic Vectors
Humans
Immunotherapy, Adoptive
/ methods
Mice
Mice, Inbred NOD
Mice, Transgenic
Neoplasms
/ genetics
Receptors, Antigen, T-Cell, alpha-beta
/ genetics
T-Lymphocytes
/ immunology
Tissue Donors
Transduction, Genetic
Xenograft Model Antitumor Assays
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
05
03
2019
revised:
06
03
2019
accepted:
07
03
2019
entrez:
17
3
2019
pubmed:
17
3
2019
medline:
17
3
2019
Statut:
epublish
Résumé
Adoptive transfer of TCR transgenic T cells holds great promise for treating various cancers. So far, mainly semi-randomly integrating vectors have been used to genetically modify T cells. These carry the risk of insertional mutagenesis, and the sole addition of an exogenous TCR potentially results in the mispairing of TCR chains with endogenous ones. Established approaches using nonviral vectors, such as transposons, already reduce the risk of insertional mutagenesis but have not accomplished site-specific integration. Here, we used CRISPR-Cas9 RNPs and adeno-associated virus 6 for gene targeting to deliver an engineered TCR gene specifically to the TCR alpha constant locus, thus placing it under endogenous transcriptional control. Our data demonstrate that this approach replaces the endogenous TCR, functionally redirects the edited T cells' specificity in vitro
Identifiants
pubmed: 30877233
pii: 2/2/e201900367
doi: 10.26508/lsa.201900367
pmc: PMC6421629
pii:
doi:
Substances chimiques
Receptors, Antigen, T-Cell, alpha-beta
0
CRISPR-Associated Protein 9
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Research Council
ID : 322865
Pays : International
Informations de copyright
© 2019 Albers et al.
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