A humanized monoclonal antibody targeting CD39 with novel mechanism for cancer treatment

Medicine in Drug Discovery

Chengbin Wu¹  Fang Ren²  Beilei Shi²  Zheng Wei²  Shiyong Gong²  Kedong Ouyang² 

[1] Corresponding 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, China;

关键词: CD39;    ATP;    Adenosine;    Xenograft;    mAb;    Tumor;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown