Nature Communications (Nov 2019)

Repurposing endogenous immune pathways to tailor and control chimeric antigen receptor T cell functionality

  • Mohit Sachdeva,
  • Brian W. Busser,
  • Sonal Temburni,
  • Billal Jahangiri,
  • Anne-Sophie Gautron,
  • Alan Maréchal,
  • Alexandre Juillerat,
  • Alan Williams,
  • Stéphane Depil,
  • Philippe Duchateau,
  • Laurent Poirot,
  • Julien Valton

DOI
https://doi.org/10.1038/s41467-019-13088-3
Journal volume & issue
Vol. 10, no. 1
pp. 1 – 16

Abstract

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Engineered T cells work as living therapeutics, but are prone to hyperreactivity and exhaustion. Here the authors improve CAR T cell antitumor responses by simultaneously targeting a CAR to TCR locus and IL-12 to PD1 locus, placing the transgenes under a naturally regulated transcriptional network while disrupting unwanted signals.