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

Kevin Sek; Lev M Kats; Phillip K Darcy; Paul A Beavis

doi:10.1016/j.coph.2020.07.002

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

Curr Opin Pharmacol. 2020 Aug:53:91-97. doi: 10.1016/j.coph.2020.07.002. Epub 2020 Aug 24.

Authors

Kevin Sek¹, Lev M Kats², Phillip K Darcy³, Paul A Beavis⁴

Affiliations

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.
² Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3010, 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].
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].

PMID: 32854024
DOI: 10.1016/j.coph.2020.07.002

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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Adenosine / immunology*
Animals
Gene Editing*
Humans
Immunotherapy, Adoptive*
Neoplasms / genetics
Neoplasms / immunology
Neoplasms / therapy*
Receptors, Chimeric Antigen*
T-Lymphocytes / immunology
Tumor Microenvironment / immunology

Substances

Receptors, Chimeric Antigen
Adenosine