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Development of CD73 Inhibitors in Tumor Immunotherapy and Opportunities in Imaging and Combination Therapy
Chunyang Bi1,2, Jimmy S Patel1,3, Steven H Liang1,4
1Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia 30322, United States.
Abstract:
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.
Insights
CD73 inhibitors are emerging as a promising approach in tumor immunotherapy. These inhibitors are advancing through clinical trials, showing potential for combination therapies and improved cancer treatment strategies.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- CD73 is an enzyme that generates adenosine, an immunosuppressive molecule.
- CD73 is overexpressed in various tumors, contributing to the tumor immune microenvironment.
- Adenosine produced by CD73 can suppress anti-tumor immunity.
Purpose of the Study:
- To review the landscape of CD73 inhibitors for cancer immunotherapy.
- To highlight the therapeutic potential of targeting CD73 in oncology.
- To discuss the role of CD73-specific imaging ligands in drug development.
Main Methods:
- Review of preclinical and clinical studies on CD73 inhibitors.
- Analysis of current clinical trial data for CD73-targeted therapies.
- Exploration of diagnostic and prognostic applications of CD73 imaging.
Main Results:
- Numerous CD73 inhibitors, including monoclonal antibodies and small molecules, are under development.
- 18 CD73 inhibitors are in clinical trials, demonstrating promising efficacy in combination therapies for solid tumors.
- CD73-specific imaging ligands offer potential for patient selection and treatment monitoring.
Conclusions:
- Targeting CD73 represents a promising strategy for novel cancer immunotherapy.
- Combination therapies involving CD73 inhibitors show significant potential in treating various solid tumors.
- Development of CD73 imaging ligands can aid in the clinical translation of CD73-targeted therapeutics.
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