Immuno-Oncology Drug Discovery: A CD39 Activity Assay for a Promising Target
What comes to mind when you think of immunotherapy? The immune system, with all its complexities, contributes to numerous diseases that affect our society. It’s no wonder scientists scramble to find therapies that will either suppress (suppression immunotherapies) or activate (activation immunotherapies) an immune response. Immunotherapy isn’t only used for autoimmune diseases or infectious disease. As more insight into the role that the immune system plays in cancer becomes available, more immunotherapies to treat cancer have also surfaced. Researchers are constantly searching for biological connections to fight unwanted disease and when it comes to immunotherapy, they have found CD39.
The Role of CD39 in Immunotherapy
CD39 (Cluster of Differentiation 39) is an ectonucleotidase (enzyme that catalyzes the formation of nucleosides) that regulates adenosine via dephosphorylation of ATP (adenosine triphosphate). This regulatory protein can be found in a variety of cell types including tumor cells. 1 Turns out, regulating adenosine is an extremely significant responsibility as it is not only an abundant molecule inside the body and a building block for DNA, but is also used in treating a range of ailments. Equally, ATP is ever present with many functions throughout the body as well.
Maintaining a balance between the two is key when it comes to immune response as adenosine is an immune suppressor while ATP activates the immune response.2 An example of this intricate purinergic signaling pathway is when a cancer cell breaks down leaving ATP in the extracellular matrix forcing CD39 to do its job; catalyzing the reaction that produces adenosine. Although this is a simplified explanation, it elucidates the role that CD39 plays in the immune response; therefore, shows the potential of being used in immunotherapy.
How Can a CD39 Activity Assay Help?
In fact, multiple studies have found that blocking CD39 enhanced the immune response in cancer cells.1 This being the case, there are still challenges to overcome. One such challenge is maintaining the balance between ATP and adenosine since isn’t as straight forward as scientists would like. In addition, there are other molecules in the same signaling pathway that could assist and possibly improve the inhibiting effects of CD39, while increasing the immune response. Research is still needed. Fortunately, there a CD39 activity assay to assist researchers in understanding the challenges as well as gaining more knowledge in using CD39 as a target for immunotherapy. The Transcreener AMP² CD39 Activity Assay can be used as a screening tool to find novel CD39 inhibitors, thus accelerating drug discovery for this exciting emerging target.
References
- Leone RD, Emens LA. Targeting adenosine for cancer immunotherapy. 2018:1-9. https://jitc.biomedcentral.com/articles/10.1186/s40425-018-0360-8
- Zhao H, Bo C, Kang Y, Li H. What Else Can CD39 Tell Us? 2017;8(June):1-10. doi:10.3389/fimmu.2017.00727. https://www.frontiersin.org/articles/10.3389/fimmu.2017.00727/full
