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Optimism for A2A

Why two negative readouts haven't dimmed hope for A2A in cancer

Once considered solely a neurology target, the adenosine pathway has attracted interest in immuno-oncology based on its ability to control whether immune cells adopt a stimulatory or suppressive phenotype. The early results from A2A receptor antagonists first developed for neurological disease are a mixed bag. But several companies are persevering with new approaches intended to boost efficacy.

Sosei Group Corp. EVP and Chief R&D Officer Malcolm Weir told BioCentury the presence of A2A receptors on immune cells had been known for over a decade, but “it was with the advent of checkpoint inhibitors that the potential for clinical significance of this mechanism flourished.”

When adenosine binds to the adenosine A2A receptor (ADORA2A), CD8+ T cells and other lymphocytes decrease production of pro-inflammatory cytokines and increase production of immunosuppressive ones.

A2A receptor activation also up-regulates other immune checkpoints on

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