A2aR antagonists

Next generation checkpoint blockade for cancer immunotherapy

Research output: Contribution to journalArticle

Abstract

The last several years have witnessed exciting progress in the development of immunotherapy for the treatment of cancer. This has been due in great part to the development of so-called checkpoint blockade. That is, antibodies that block inhibitory receptors such as CTLA-4 and PD-1 and thus unleash antigen-specific immune responses against tumors. It is clear that tumors evade the immune response by usurping pathways that play a role in negatively regulating normal immune responses. In this regard, adenosine in the immune microenvironment leading to the activation of the A2a receptor has been shown to represent one such negative feedback loop. Indeed, the tumor microenvironment has relatively high concentrations of adenosine. To this end, blocking A2a receptor activation has the potential to markedly enhance anti-tumor immunity in mouse models. This review will present data demonstrating the ability of A2a receptor blockade to enhance tumor vaccines, checkpoint blockade and adoptive T cell therapy. Also, as several recent studies have demonstrated that under certain conditions A2a receptor blockade can enhance tumor progression, we will also explore the complexities of adenosine signaling in the immune response. Despite important nuances to the A2a receptor pathway that require further elucidation, studies to date strongly support the development of A2a receptor antagonists (some of which have already been tested in phase III clinical trials for Parkinson Disease) as novel modalities in the immunotherapy armamentarium.

Original languageEnglish (US)
Pages (from-to)265-272
Number of pages8
JournalComputational and Structural Biotechnology Journal
Volume13
DOIs
StatePublished - 2015

Fingerprint

Immunotherapy
Tumors
Adenosine
Neoplasms
Chemical activation
Phase III Clinical Trials
Cancer Vaccines
Tumor Microenvironment
T-cells
Histocompatibility Antigens Class II
Cell- and Tissue-Based Therapy
Vaccines
Parkinson Disease
Antigens
Immunity
Antibodies
T-Lymphocytes
Feedback
Therapeutics

Keywords

  • A2a adenosine receptor
  • Immune checkpoint
  • Immunotherapy
  • PD-1
  • T cell
  • Tumor

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Biophysics
  • Structural Biology
  • Genetics
  • Computer Science Applications

Cite this

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title = "A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy",
abstract = "The last several years have witnessed exciting progress in the development of immunotherapy for the treatment of cancer. This has been due in great part to the development of so-called checkpoint blockade. That is, antibodies that block inhibitory receptors such as CTLA-4 and PD-1 and thus unleash antigen-specific immune responses against tumors. It is clear that tumors evade the immune response by usurping pathways that play a role in negatively regulating normal immune responses. In this regard, adenosine in the immune microenvironment leading to the activation of the A2a receptor has been shown to represent one such negative feedback loop. Indeed, the tumor microenvironment has relatively high concentrations of adenosine. To this end, blocking A2a receptor activation has the potential to markedly enhance anti-tumor immunity in mouse models. This review will present data demonstrating the ability of A2a receptor blockade to enhance tumor vaccines, checkpoint blockade and adoptive T cell therapy. Also, as several recent studies have demonstrated that under certain conditions A2a receptor blockade can enhance tumor progression, we will also explore the complexities of adenosine signaling in the immune response. Despite important nuances to the A2a receptor pathway that require further elucidation, studies to date strongly support the development of A2a receptor antagonists (some of which have already been tested in phase III clinical trials for Parkinson Disease) as novel modalities in the immunotherapy armamentarium.",
keywords = "A2a adenosine receptor, Immune checkpoint, Immunotherapy, PD-1, T cell, Tumor",
author = "Robert Leone and Lo, {Ying Chun} and Jonathan Powell",
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