Loading...
Targeted T cell receptor gene editing provides predictable T cell product function for immunotherapy.
Müller, Thomas R Jarosch, Sebastian Hammel, Monika Leube, Justin Grassmann, Simon Bernard, Bettina Effenberger, Manuel Andrä, Immanuel Chaudhry, M Zeeshan Käuferle, Theresa
Müller, Thomas R
Jarosch, Sebastian
Hammel, Monika
Leube, Justin
Grassmann, Simon
Bernard, Bettina
Effenberger, Manuel
Andrä, Immanuel
Chaudhry, M Zeeshan
Käuferle, Theresa
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2021-08-17
Submitted date
Files
Loading...
Open Access publication
Adobe PDF, 4.12 MB
Other Titles
Abstract
Adoptive transfer of T cells expressing a transgenic T cell receptor (TCR) has the potential to revolutionize immunotherapy of infectious diseases and cancer. However, the generation of defined TCR-transgenic T cell medicinal products with predictable in vivo function still poses a major challenge and limits broader and more successful application of this "living drug." Here, by studying 51 different TCRs, we show that conventional genetic engineering by viral transduction leads to variable TCR expression and functionality as a result of variable transgene copy numbers and untargeted transgene integration. In contrast, CRISPR/Cas9-mediated TCR replacement enables defined, targeted TCR transgene insertion into the TCR gene locus. Thereby, T cell products display more homogeneous TCR expression similar to physiological T cells. Importantly, increased T cell product homogeneity after targeted TCR gene editing correlates with predictable in vivo T cell responses, which represents a crucial aspect for clinical application in adoptive T cell immunotherapy.
Citation
Cell Rep Med. 2021 Aug 17;2(8):100374. doi: 10.1016/j.xcrm.2021.100374.
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
EISSN
2666-3791
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution-NonCommercial-NoDerivatives 4.0 International