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Monitoring and characterizing soluble and membrane-bound ectonucleotidases CD73 and CD39

View ORCID ProfileSaid A. Goueli, Kevin Hsiao
doi: https://doi.org/10.1101/698373
Said A. Goueli
Department of Cell Signaling, Research and Development, Promega Corp. Madison WI 53711
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  • For correspondence: Said.goueli@promega.com
Kevin Hsiao
Department of Cell Signaling, Research and Development, Promega Corp. Madison WI 53711
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Abstract

The success of immunotherapy treatment in oncology ushered a new modality for treating a wide variety of cancers. However, lack of effect in some patients made it imperative to identify other pathways that are exploited by cancer cells to circumvent immune surveillance, and possibly synergize immune checkpoint treatment in those cases. It has been recently recognized that adenosine levels increased significantly in the tumor microenvironment and that adenosine/adenosine receptors play a powerful role as immunosuppressant and attenuating several effector T cell functions. The two main enzymes responsible for generating adenosine in the microenvironment are the ectonucleotidases CD39 and CD73, the former utilizes both ATP and ADP and producing AMP while the latter utilizes AMP and generates adenosine. Thus, these two enzymes combined are the major source for the bulk of adenosine produced in the microenvironment. They were shown to be validated targets in oncology leading to several clinical trials that include small molecules as well as antibodies, showing positive and encouraging results in the preclinical arena. Towards the development of novel drugs to target these enzymes, we have developed a platform that can be utilized to monitor the activities of both enzymes in vitro (biochemical) as well as in cells (cell based) assays. We have developed very sensitive and homogenous assays that enabled us to monitor the activity of both enzymes and demonstrate selectivity of known inhibitors as well as monoclonal antibodies. This should speed up screening for novel inhibitors leading to more effective cancer therapy

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 10, 2019.
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Monitoring and characterizing soluble and membrane-bound ectonucleotidases CD73 and CD39
Said A. Goueli, Kevin Hsiao
bioRxiv 698373; doi: https://doi.org/10.1101/698373
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Monitoring and characterizing soluble and membrane-bound ectonucleotidases CD73 and CD39
Said A. Goueli, Kevin Hsiao
bioRxiv 698373; doi: https://doi.org/10.1101/698373

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