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Pharmacological and genetic strategies for targeting adenosine to enhance adoptive T cell therapy of cancer.

Authors
  • Sek, Kevin1
  • Kats, Lev M2
  • Darcy, Phillip K3
  • Beavis, Paul A4
  • 1 Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, 3000, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3010, Australia. , (Australia)
  • 2 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3010, Australia. , (Australia)
  • 3 Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, 3000, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3010, Australia; Department of Pathology, University of Melbourne, Parkville, Australia; Department of Immunology, Monash University, Clayton, Australia. Electronic address: [email protected] , (Australia)
  • 4 Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, 3000, Victoria, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3010, Australia. Electronic address: [email protected] , (Australia)
Type
Published Article
Journal
Current opinion in pharmacology
Publication Date
Aug 24, 2020
Volume
53
Pages
91–97
Identifiers
DOI: 10.1016/j.coph.2020.07.002
PMID: 32854024
Source
Medline
Language
English
License
Unknown

Abstract

Adoptive cellular therapy involves the ex vivo expansion of immune cells, conventionally T cells, before reinfusion back to the patient. Variations in adoptive cellular therapy include transduction of a patient's T cells with either a transgenic T cell receptor or chimeric antigen receptor (CAR) to recognize a defined tumor antigen. Given that adenosine is a major axis of immunosuppression of T cells, particularly in hypoxic tumor microenvironments, therapeutics targeting this pathway are currently being assessed for their potential to enhance adoptive T cell therapies. The use of gene-editing technology, commonly used in tandem with CAR and transgenic T cell receptor (TCR) based adoptive cellular therapy, offers further opportunities to specifically modulate responses to adenosine. This review will discuss recent advances in targeting the adenosine pathway for enhancing the effectiveness of adoptive cellular therapy in the treatment of solid cancers. Copyright © 2020 Elsevier Ltd. All rights reserved.

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