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