Unlocking the Potential of RVU330: A Dual A2A/A2B Antagonist for Cancer Immunotherapy

Researchers are focusing on the immunosuppressive effects of adenosine as a potential target for cancer treatment. Adenosine is found in high levels in various tumor types and impacts immune cells such as T lymphocytes, dendritic cells, and macrophages. It signals through A2A or A2B receptors, suggesting that blocking both receptors could be highly effective in countering adenosine's immunosuppressive effects.

Our study introduces the dual A2A/A2B antagonist RVU330, which shows significant potency in environments rich in adenosine, similar to those found in tumors. When compared to other compounds in clinical development, RVU330 has demonstrated superior characteristics. It maintains potent antagonistic activity against both receptors even in high adenosine conditions. Extensive pharmacological evaluations, from receptor binding to functional assays using primary human immune cells, have shown RVU330's ability to reverse adenosine-induced immune suppression. It has been particularly effective in enhancing the activity of CD4+ and CD8+ T-cells, monocyte-derived dendritic cells, and macrophages. The compound's high activity in human whole blood assays indicates that low concentrations can effectively counter adenosine. The therapeutic efficacy of RVU330 has been validated in mouse models, and it is currently undergoing further preclinical evaluation.

RVU330 stands out due to its dual antagonistic profile and its capacity to inhibit both receptors under high adenosine conditions, which are distinguishing features compared to other adenosine receptor antagonists. The research was presented at the Annual Meeting of the American Association for Cancer Research in 2020.