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Targeting Adenosine with Adenosine Deaminase 2 to Inhibit Growth of Solid Tumors

Cancer Res. 2021-04; 
Lin Wang, Luz M Londono, Jessica Cowell, Ozge Saatci, Mertkaya Aras, Pelin G Ersan, Sara Serra, Hong Pei, Renee Clift, Qiping Zhao, Kim B Phan, Lei Huang, Michael J LaBarre, Xiaoming Li, H Michael Shepard, Silvia Deaglio, Joel Linden, Christopher D Thanos, Ozgur Sahin, Caglar Cekic
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Mutagenesis Services Variants were generated using the QuickChange Lightning Multi Site-Directed Mutagenesis Kit (catalog no. 210518; Agilent Technologies) and were expressed in Chinese hamster ovary-suspension cells. FLAG-tagged ADA2 variants were purified using an anti-FLAG M2 affinity resin (catalog no. L00432; GenScript). Get A Quote


Extracellular adenosine in tumors can suppress immune responses and promote tumor growth. Adenosine deaminase 2 (ADA2) converts adenosine into inosine. The role of ADA2 in cancer and whether it can target adenosine for cancer therapy has not been investigated. Here we show that increased ADA2 expression is associated with increased patient survival and enrichment of adaptive immune response pathways in several solid tumor types. Several ADA2 variants were created to improve catalytic efficiency, and PEGylation was used to prolong systemic exposure. In mice, PEGylated ADA2 (PEGADA2) inhibited tumor growth by targeting adenosine in an enzyme activity-dependent manner and thereby modulating immune responses. These... More