Specificity
CD73 is a membrane-bound extracellular enzyme overexpressed in several cancer types. Its expression has been linked to poor prognosis in melanoma, colorectal, gastric, triple negative breast cancer, and to a pro-metastatic phenotype in prostate cancer. Together with CD39, it plays a major role in promoting immunosuppression through the pathway degrading adenosine triphosphate (ATP) into adenosine. Within the tumor microenvironment, ATP promotes immune cell-mediated killing of cancer cells. In contrast, adenosine accumulation causes immune suppression, dysregulation of immune cell infiltrates and stimulates angiogenesis resulting in tumor spreading. CD73 is active on the last step of the degradation pathway, where it is the enzyme that actually degrades AMP into adenosine. CD73-blockade promotes anti-tumor immunity by reducing adenosine accumulation. Accordingly, anti-CD73 mAbs stimulate anti-tumor immunity and reduce tumor metastasis in mouse tumor models, and could enhance the efficacy of treatment with anti-PD1 or anti-CTLA4 antibodies.