Advancements in Immuno-Oncology: The Role of EOS100850 in Targeting T Cell Suppression and Enhancing Anti-Tumor Response

The study focuses on the role of extracellular adenosine in the tumor microenvironment and its impact on immune evasion. It has been found that adenosine, particularly through the A2A receptor (A2AR), can suppress the immune response by decreasing cytokine production in T cells and monocytes, as well as the cytotoxic activity of T and NK cells. The research highlights that A2AR antagonists, initially developed for Parkinson's disease, lose their effectiveness in an environment with high adenosine levels.

To address this challenge, a new compound, EOS100850, was developed. This compound is a highly selective A2AR inhibitor with a sub-nanomolar Ki and does not penetrate the brain. It has been shown to effectively inhibit A2AR signaling in human T lymphocytes, even in the presence of high adenosine concentrations, and to restore cytokine production.

EOS100850 was also tested in an in vivo assay using mice, where it demonstrated a significant inhibition of pCREB, a marker of A2AR activation. Notably, the compound's pharmacodynamic activity lasted longer than its presence in the plasma, indicating a prolonged effect.

In a mouse A20 lymphoma model, EOS100850, when combined with anti-PD-L1, significantly suppressed tumor growth compared to anti-PD-L1 alone. The compound is described as a potent, insurmountable, and best-in-class A2AR blocker, specifically optimized for use in immuno-oncology.

The abstract concludes by citing the research in the context of the American Association for Cancer Research Annual Meeting 2018, emphasizing the potential of EOS100850 for further study and development in human cancer treatment.