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

作　　者：Yuhan Li Xiangqing Ding Xianxian Wu Longfei Ding Yuhui Yang Xiaoliang Jiang Xing Liu Xu Zhang Jianrong Su Jianqing Xu Zhiwei Yang 

机构地区：[1]Institute of Laboratory Animal Science,Chinese Academy of Medical Sciences(CAMS)&Comparative Medicine Centre,Peking Union Medical College(PUMC),Beijing 100021,China [2]Department of Clinical Laboratory,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China [3]Shanghai Sinobay Biotechnology Company(Limited),Shanghai 201500,China [4]Shanghai Public Health Clinical Center,Fudan University,Shanghai 200083,China [5]Capital Medical University,Beijing 100069,China [6]Department of Hepatobiliary Pancreatic Surgery,Zhengzhou University People's Hospital,Henan Provincial People's Hospital,Zhengzhou 450003,China [7]Chongqing Institutes for Life Science Innovation,Chongqing 400715,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第11期4461-4476,共16页药学学报（英文版）

基　　金：supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CAMS,2021-I2M1-072,China);National Natural Science Foundation of China (82161138027 and 81970358)。

摘　　要：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 effects.In 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 macaques.We 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 vitro.In vivo,we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and L-arginine induced AP models.We also evaluated the safety profile after RH001-6 treatment in mice,and verified that RH001-6 did not cause any significant pathological damages in vivo.Taken 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 AP.Therefore,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 

分 类 号：R57[医药卫生—消化系统]