Nature Communications (May 2021)

CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy

  • Lauren Giuffrida,
  • Kevin Sek,
  • Melissa A. Henderson,
  • Junyun Lai,
  • Amanda X. Y. Chen,
  • Deborah Meyran,
  • Kirsten L. Todd,
  • Emma V. Petley,
  • Sherly Mardiana,
  • Christina Mølck,
  • Gregory D. Stewart,
  • Benjamin J. Solomon,
  • Ian A. Parish,
  • Paul J. Neeson,
  • Simon J. Harrison,
  • Lev M. Kats,
  • Imran G. House,
  • Phillip K. Darcy,
  • Paul A. Beavis

DOI
https://doi.org/10.1038/s41467-021-23331-5
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 18

Abstract

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Activation of the adenosine receptor A2AR is associated with suppression of T cell function in the tumor microenvironment. To overcome immunosuppression, here the authors show that CRISPR/Cas9 mediated deletion of A2AR enhances CAR T cell effector functions without altering memory or persistence properties, improving CAR-T mediated tumor control in pre-clinical models.