TCR sequencing and cloning methods for repertoire analysis and isolation of tumor-reactive TCRs.
T cell engineering
T cell receptor
TCR cloning
TCR repertoire
cancer
immune diversity
immune repertoire
immunotherapy
repertoire profiling
Journal
Cell reports methods
ISSN: 2667-2375
Titre abrégé: Cell Rep Methods
Pays: United States
ID NLM: 9918227360606676
Informations de publication
Date de publication:
24 04 2023
24 04 2023
Historique:
received:
17
10
2022
revised:
27
02
2023
accepted:
27
03
2023
medline:
11
5
2023
pubmed:
9
5
2023
entrez:
9
5
2023
Statut:
epublish
Résumé
T cell receptor (TCR) technologies, including repertoire analyses and T cell engineering, are increasingly important in the clinical management of cellular immunity in cancer, transplantation, and other immune diseases. However, sensitive and reliable methods for repertoire analyses and TCR cloning are still lacking. Here, we report on SEQTR, a high-throughput approach to analyze human and mouse repertoires that is more sensitive, reproducible, and accurate as compared with commonly used assays, and thus more reliably captures the complexity of blood and tumor TCR repertoires. We also present a TCR cloning strategy to specifically amplify TCRs from T cell populations. Positioned downstream of single-cell or bulk TCR sequencing, it allows time- and cost-effective discovery, cloning, screening, and engineering of tumor-specific TCRs. Together, these methods will accelerate TCR repertoire analyses in discovery, translational, and clinical settings and permit fast TCR engineering for cellular therapies.
Identifiants
pubmed: 37159666
doi: 10.1016/j.crmeth.2023.100459
pii: S2667-2375(23)00078-4
pmc: PMC10163020
doi:
Substances chimiques
Receptors, Antigen, T-Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100459Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The University of Lausanne and Ludwig Institute for Cancer Research have filed for patent protection on the technology described herein. R.G. is named as inventor on this patent. G.C. has received grants from Celgene, Boehringer-Ingelheim, Roche, Bristol Myers Squibb, Iovance Therapeutics, and Kite Pharma. The institution with which G.C. is affiliated has received fees for G.C.’s participation on advisory boards or for presentation at a company-sponsored symposium from Genentech, Roche, Bristol Myers Squibb, AstraZeneca, NextCure, Geneos Tx, and Sanofi/Avensis. The Center Hospitalier Universitaire Vaudois (CHUV) and the Ludwig Institute for Cancer Research have filed for patent protection on the technology related to T cell expansion. S.B., A.H., and G.C. are named as inventors on this patent. G.C. has patents in the domain of antibodies and vaccines targeting the tumor vasculature as well as technologies related to T cell engineering for T cell therapy. G.C. holds patents around antibodies and receives royalties from the University of Pennsylvania regarding technology licensed to Novartis.
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