On the mechanism of anti-CD39 immune checkpoint therapy
With the coming of age of cancer immunotherapy, the search for new therapeutic targets has led to the identification of immunosuppressive adenosine as an important regulator of antitumor immunity. This resulted in the development of selective inhibitors targeting various components of the adenosiner...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000186.full |
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| author | John Stagg Bertrand Allard David Allard |
| author_facet | John Stagg Bertrand Allard David Allard |
| author_sort | John Stagg |
| collection | DOAJ |
| description | With the coming of age of cancer immunotherapy, the search for new therapeutic targets has led to the identification of immunosuppressive adenosine as an important regulator of antitumor immunity. This resulted in the development of selective inhibitors targeting various components of the adenosinergic pathway, including small molecules antagonists targeting the high affinity A2A adenosine receptor and low affinity A2B receptor, therapeutic monoclonal antibodies (mAbs) and small molecules targeting CD73 and therapeutic mAbs targeting CD39. As each regulator of the adenosinergic pathway present non-overlapping biologic functions, a better understanding of the mechanisms of action of each targeted approach should accelerate clinical translation and improve rational design of combination treatments. In this review, we discuss the potential mechanisms-of-action of anti-CD39 cancer therapy and potential toxicities that may emerge from sustained CD39 inhibition. Caution should be taken, however, in extrapolating data from gene-targeted mice to patients treated with blocking anti-CD39 agents. As phase I clinical trials are now underway, further insights into the mechanism of action and potential adverse events associated with anti-CD39 therapy are anticipated in coming years. |
| format | Article |
| id | doaj-art-ef83d9f96a6a4ad79cfe56774d65ca6a |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-ef83d9f96a6a4ad79cfe56774d65ca6a2025-08-20T02:13:12ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2019-000186On the mechanism of anti-CD39 immune checkpoint therapyJohn Stagg0Bertrand Allard1David Allard2CHUM Research Centre, Université de Montréal, Montreal, QC, CanadaAff1 grid.14848.310000000122923357CRCHUM, Montreal Cancer InstituteMontreal University Montréal PQ CanadaFaculty of Pharmacy, Centre Hospitalier de L`Universite de Montreal, Montreal, Quebec, CanadaWith the coming of age of cancer immunotherapy, the search for new therapeutic targets has led to the identification of immunosuppressive adenosine as an important regulator of antitumor immunity. This resulted in the development of selective inhibitors targeting various components of the adenosinergic pathway, including small molecules antagonists targeting the high affinity A2A adenosine receptor and low affinity A2B receptor, therapeutic monoclonal antibodies (mAbs) and small molecules targeting CD73 and therapeutic mAbs targeting CD39. As each regulator of the adenosinergic pathway present non-overlapping biologic functions, a better understanding of the mechanisms of action of each targeted approach should accelerate clinical translation and improve rational design of combination treatments. In this review, we discuss the potential mechanisms-of-action of anti-CD39 cancer therapy and potential toxicities that may emerge from sustained CD39 inhibition. Caution should be taken, however, in extrapolating data from gene-targeted mice to patients treated with blocking anti-CD39 agents. As phase I clinical trials are now underway, further insights into the mechanism of action and potential adverse events associated with anti-CD39 therapy are anticipated in coming years.https://jitc.bmj.com/content/8/1/e000186.full |
| spellingShingle | John Stagg Bertrand Allard David Allard On the mechanism of anti-CD39 immune checkpoint therapy Journal for ImmunoTherapy of Cancer |
| title | On the mechanism of anti-CD39 immune checkpoint therapy |
| title_full | On the mechanism of anti-CD39 immune checkpoint therapy |
| title_fullStr | On the mechanism of anti-CD39 immune checkpoint therapy |
| title_full_unstemmed | On the mechanism of anti-CD39 immune checkpoint therapy |
| title_short | On the mechanism of anti-CD39 immune checkpoint therapy |
| title_sort | on the mechanism of anti cd39 immune checkpoint therapy |
| url | https://jitc.bmj.com/content/8/1/e000186.full |
| work_keys_str_mv | AT johnstagg onthemechanismofanticd39immunecheckpointtherapy AT bertrandallard onthemechanismofanticd39immunecheckpointtherapy AT davidallard onthemechanismofanticd39immunecheckpointtherapy |