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AZD4635, a novel adenosine A2A receptor antagonist, restores anti-tumor activity by preventing adenosine-mediated suppression of immune cells (AACR 2019)

By AstraZeneca | Apr 14, 2019

Conference

AACR Annual Meeting 2019
29 March – 3 April 2019
Atlanta, U.S.
American Association for Cancer Research
Conference Website

Summary

AstraZeneca presented new data from preclinical studies with AZD4635, a next-generation immuno-oncology candidate, demonstrating its ability to restore the anti-tumor activity of dendritic cells (DCs) by preventing their adenosine-mediated immunosuppression. The new data were presented in a poster at the 2019 American Association for Cancer Research (AACR) Annual Meeting in Atlanta, USA (29 March to 3 April 2019).

Dendritic cells are a key component of the immune system that drive anti-tumor activity through the stimulation and promotion of tumor-specific T cell responses. The activity of DCs is suppressed in the presence of high levels of adenosine, which is part of a normal process preventing autoimmunity and is co-opted by tumors as an immune escape mechanism. The adenosine pathway is increasingly recognized as critical to tumor suppression and represents a new frontier within immuno-oncology.

AZD4635 is a potent and selective, orally available, small molecule adenosine 2A receptor (A2AR) antagonist discovered by Sosei Heptares and exclusively licensed to AstraZeneca in 2015.

Poster Summary

The poster (abstract #LB-192) entitled “The A2AR antagonist AZD4635 prevents adenosine-mediated immunosuppression of CD103+ dendritic cells,” reported the following:

  • In vitro studies using an adenosine analog disrupts normal function in both mouse and human DCs in differentiating and priming naïve T cells and therefore driving antigen-specific tumor cytotoxic T cell responses under conditions of high extracellular adenosine.
  • AZD4635 restored DC function in the stimulation and promotion of antigen-specific T cell responses.
  • Adenosine antagonism by AZD4635 improved antigen presentation and co-stimulation by DCs, leading to better priming and expansion of antigen specific T cells.
  • AZD4635 prevented adenosine-mediated immuno-suppression of critical aspects of DC phenotype and function in vitro.

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