Development of CD73 Inhibitors in Tumor Immunotherapy and Opportunities in Imaging and Combination Therapy

CD73 is a member of the membrane-bound enucleotidase family, which catalyzes the extracellular hydrolysis of adenosine monophosphate (AMP) to produce anti-inflammatory and immunosuppressive adenosine. As a novel checkpoint protein, CD73 is overexpressed in the immune system of various tumors, where adenosine is abundantly enriched. A large number of monoclonal antibodies (mAbs), nucleotides, and non-nucleotides as potent CD73 inhibitors are being discovered, providing opportunities for novel tumor immunotherapy. Currently, 18 CD73 inhibitors are in clinical trials, showing promising results in combination therapy for various solid tumors. The development of CD73-specific companion positron emission tomography imaging ligands holds potential for facilitating diagnosis, patient selection, and treatment efficacy evaluation throughout the entire process of CD73-targeted therapeutic development.