A humanized monoclonal antibody targeting CD39 with novel mechanism for cancer treatment
ATP-adenosine signal axis plays an import role in tumor immune regulation. ATP released by tumor cells can promote antitumor immunity, and adenosine can suppress the immune response. CD39, also known as Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), can hydrolyze ATP into ADP and AMP, then...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-09-01
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| Series: | Medicine in Drug Discovery |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590098621000142 |
| _version_ | 1818881065535668224 |
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| author | Zheng Wei Fang Ren Shiyong Gong Beilei Shi Kedong Ouyang Chengbin Wu |
| author_facet | Zheng Wei Fang Ren Shiyong Gong Beilei Shi Kedong Ouyang Chengbin Wu |
| author_sort | Zheng Wei |
| collection | DOAJ |
| description | ATP-adenosine signal axis plays an import role in tumor immune regulation. ATP released by tumor cells can promote antitumor immunity, and adenosine can suppress the immune response. CD39, also known as Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), can hydrolyze ATP into ADP and AMP, then transfer AMP to immunosuppressive adenosine. High expression of CD39 in tumor microenvironment (TME) disrupted the balance of pro-inflammation and anti-inflammation, attributed by ATP-adenosine metabolism. In order to evaluate the potency of targeting CD39 as a novel anti-tumor therapy, we generated a fully humanized anti-CD39 mAb, EMB04. In vitro and in vivo characterization of EMB04 demonstrated that EMB04 can efficiently block the ATPase activity of membrane-associated and soluble CD39 protein. EMB04 also suppressed tumor growth in the xenograft model of SCID mice. In summary, EMB04 is a potent highly efficient inhibitor of CD39 ATPase activity that may contribute to future immunotherapy for cancer. |
| first_indexed | 2024-12-19T14:55:56Z |
| format | Article |
| id | doaj.art-b267abb1e8cb47589e1ac99582ab2c09 |
| institution | Directory Open Access Journal |
| issn | 2590-0986 |
| language | English |
| last_indexed | 2024-12-19T14:55:56Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Medicine in Drug Discovery |
| spelling | doaj.art-b267abb1e8cb47589e1ac99582ab2c092022-12-21T20:16:43ZengElsevierMedicine in Drug Discovery2590-09862021-09-0111100093A humanized monoclonal antibody targeting CD39 with novel mechanism for cancer treatmentZheng Wei0Fang Ren1Shiyong Gong2Beilei Shi3Kedong Ouyang4Chengbin Wu5EpimAb Biotherapeutics Inc., 4560 Jinke Rd. Building 2, Shanghai, ChinaEpimAb Biotherapeutics Inc., 4560 Jinke Rd. Building 2, Shanghai, ChinaEpimAb Biotherapeutics Inc., 4560 Jinke Rd. Building 2, Shanghai, ChinaEpimAb Biotherapeutics Inc., 4560 Jinke Rd. Building 2, Shanghai, ChinaEpimAb Biotherapeutics Inc., 4560 Jinke Rd. Building 2, Shanghai, ChinaCorresponding author at: 6th Floor, Building 2, Jinchuang Building, 702 Zhongke Road, Zhangjiang High-Tech Park, Shanghai 201204, China.; EpimAb Biotherapeutics Inc., 4560 Jinke Rd. Building 2, Shanghai, ChinaATP-adenosine signal axis plays an import role in tumor immune regulation. ATP released by tumor cells can promote antitumor immunity, and adenosine can suppress the immune response. CD39, also known as Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), can hydrolyze ATP into ADP and AMP, then transfer AMP to immunosuppressive adenosine. High expression of CD39 in tumor microenvironment (TME) disrupted the balance of pro-inflammation and anti-inflammation, attributed by ATP-adenosine metabolism. In order to evaluate the potency of targeting CD39 as a novel anti-tumor therapy, we generated a fully humanized anti-CD39 mAb, EMB04. In vitro and in vivo characterization of EMB04 demonstrated that EMB04 can efficiently block the ATPase activity of membrane-associated and soluble CD39 protein. EMB04 also suppressed tumor growth in the xenograft model of SCID mice. In summary, EMB04 is a potent highly efficient inhibitor of CD39 ATPase activity that may contribute to future immunotherapy for cancer.http://www.sciencedirect.com/science/article/pii/S2590098621000142CD39ATPAdenosineXenograftmAbTumor |
| spellingShingle | Zheng Wei Fang Ren Shiyong Gong Beilei Shi Kedong Ouyang Chengbin Wu A humanized monoclonal antibody targeting CD39 with novel mechanism for cancer treatment Medicine in Drug Discovery CD39 ATP Adenosine Xenograft mAb Tumor |
| title | A humanized monoclonal antibody targeting CD39 with novel mechanism for cancer treatment |
| title_full | A humanized monoclonal antibody targeting CD39 with novel mechanism for cancer treatment |
| title_fullStr | A humanized monoclonal antibody targeting CD39 with novel mechanism for cancer treatment |
| title_full_unstemmed | A humanized monoclonal antibody targeting CD39 with novel mechanism for cancer treatment |
| title_short | A humanized monoclonal antibody targeting CD39 with novel mechanism for cancer treatment |
| title_sort | humanized monoclonal antibody targeting cd39 with novel mechanism for cancer treatment |
| topic | CD39 ATP Adenosine Xenograft mAb Tumor |
| url | http://www.sciencedirect.com/science/article/pii/S2590098621000142 |
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