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
Affiliations
- Lauren Giuffrida
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Kevin Sek
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Melissa A. Henderson
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Junyun Lai
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Amanda X. Y. Chen
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Deborah Meyran
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Kirsten L. Todd
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Emma V. Petley
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Sherly Mardiana
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Christina Mølck
- Department of Pathology, University of Melbourne
- Gregory D. Stewart
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University
- Benjamin J. Solomon
- Sir Peter MacCallum Department of Oncology, The University of Melbourne
- Ian A. Parish
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Paul J. Neeson
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Simon J. Harrison
- Sir Peter MacCallum Department of Oncology, The University of Melbourne
- Lev M. Kats
- Sir Peter MacCallum Department of Oncology, The University of Melbourne
- Imran G. House
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Phillip K. Darcy
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- Paul A. Beavis
- Cancer Immunology Program, Peter MacCallum Cancer Centre
- DOI
- https://doi.org/10.1038/s41467-021-23331-5
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 18
Abstract
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.