Adenosine release in the tumor-microenvironment has been recently identified as a key cancer immune evasion mechanism. In 2014, a publication (Mittal D et al; Cancer Res. 2014) suggested that combining an A2aR-antagonist with an anti-PD1 monoclonal antibody was able to significantly reduce metastatic burden (also demonstrated with anti-CTLA 4 and anti-TIM 3) and to extend survival in animal cancer models. Since then, adenosine receptors have been confirmed as promising immune checkpoints to combine with existing strategies to restore immune response.
In 2017, Domain Therapeutics and Merck KGaA (Darmstadt, Germany) entered into a collaboration and licensing agreement for the development of adenosine receptors antagonist drugs specifically designed for oncology and immuno-oncology (see press release). The program entered regulatory phase of drug development in 2020 (see press release).