Modulation of TCR stimulation and pifithrin-α improves the genomic safety profile of CRISPR-engineered human T cells

Laurenz T. Ursch, Jule S. Müschen, Julia Ritter, Julia Klermund, Bettina E. Bernard, Saskia Kolb, Linda Warmuth, Geoffroy Andrieux, Gregor Miller, Marina Jiménez-Muñoz, Fabian J. Theis, Melanie Boerries, Dirk H. Busch, Toni Cathomen, Kathrin Schumann · 2024

Read Modulation of TCR stimulation and pifithrin-α improves the genomic safety profile of CRISPR-engineered human T cells by Laurenz T. Ursch, Jule S. Müschen, Julia Ritter, Julia Klermund, Bettina E. Bernard, Saskia Kolb, Linda Warmuth, Geoffroy Andrieux, Gregor Miller, Marina Jiménez-Muñoz, Fabian J. Theis, Melanie Boerries, Dirk H. Busch, Toni Cathomen, Kathrin Schumann (2024) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/pmc-11722128.txt.

Description

Laurenz Ursch and a large team of co-authors study the genomic safety of CRISPR-edited T cells in two thousand twenty-four. Such edited cells lead new cancer treatments, but CRISPR can cause large deletions and chromosome errors. Past safety work focused on the editing tools, less on the T cells themselves.

The team found that strong T cell stimulation and fast growth correlate with larger deletions. Editing quiet, non-activated cells cut that risk but lowered knockout rates. Adding a small molecule, pifithrin-alpha, also limited deletions, translocations, and chromosome count errors. It did so without hurting the cells' function, including in CAR T cells. Both strategies are easy to adopt, the authors say.

Catalog record

CREATORLaurenz T. Ursch, Jule S. Müschen, Julia Ritter, Julia Klermund, Bettina E. Bernard, Saskia Kolb, Linda Warmuth, Geoffroy Andrieux, Gregor Miller, Marina Jiménez-Muñoz, Fabian J. Theis, Melanie Boerries, Dirk H. Busch, Toni Cathomen, Kathrin Schumann
YEAR2024
COLLECTIONPAPERS
FORMATTXT
FILE SIZE80 KB
VERSION1.0
LICENSECC BY 4.0
RIGHTSCC BY
SOURCEEurope PMC

Source: https://europepmc.org/articles/PMC11722128

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