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A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses

引用

Acta Pharmaceutica Sinica B 2023年第11期13卷 4461-4476页

作者： Yuhan Li Xiangqing Ding Xianxian Wu Longfei Ding Yuhui Yang Xiaoliang Jiang Xing Liu Xu Zhang Jianrong Su Jianqing Xu Zhiwei Yang Institute of Laboratory Animal Science Chinese Academy of Medical Sciences(CAMS)&Comparative Medicine CentrePeking Union Medical College(PUMC)Beijing 100021China Department of Clinical Laboratory Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Shanghai Sinobay Biotechnology Company(Limited) Shanghai 201500China Shanghai Public Health Clinical Center Fudan UniversityShanghai 200083China Capital Medical University Beijing 100069China Department of Hepatobiliary Pancreatic Surgery Zhengzhou University People's HospitalHenan Provincial People's HospitalZhengzhou 450003China Chongqing Institutes for Life Science Innovation Chongqing 400715China

Acute pancreatitis(AP)is a devastating disease characterized by an inflammatory disorder of the pancreas.P-selectin glycoprotein ligand-1(PSGL-1)plays a crucial role in the initial steps of the adhesive at process to inflammatory sites,blockade of PSGL-1 might confer potent anti-inflammatory *** this study,we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1,RH001-6 and RH001-22,which were screened from immunized rhesus *** found that RH001-6,can effectively block the binding of P-selectin to PSGL-1,and abolish the adhesion of leukocytes to endothelial cells in *** vivo,we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and L-arginine induced AP *** also evaluated the safety profile after RH001-6 treatment in mice,and verified that RH001-6 did not cause any significant pathological damages in *** together,we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity,named RH001-6,which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during ***,RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases,such as AP.

关键词： Acute pancreatitis PSGL-1 Non-human primate Monoclonal antibody Therapeutic antibody RH001-6 adhesion of leukocytes to endothelial cells Inflammatory responses Pancreatic injury

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