A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses.
10.1016/j.apsb.2023.07.028
- Author:
Yuhan LI
1
;
Xiangqing DING
2
;
Xianxian WU
1
;
Longfei DING
3
;
Yuhui YANG
4
;
Xiaoliang JIANG
1
;
Xing LIU
1
;
Xu ZHANG
5
;
Jianrong SU
6
;
Jianqing XU
2
;
Zhiwei YANG
1
Author Information
1. Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Centre, Peking Union Medical College (PUMC), Beijing 100021, China.
2. Shanghai Sinobay Biotechnology Company (Limited), Shanghai 201500, China.
3. Shanghai Public Health Clinical Center, Fudan University, Shanghai 200083, China.
4. Capital Medical University, Beijing 100069, China.
5. Department of Hepatobiliary Pancreatic Surgery, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou 450003, China.
6. Department of Clinical Laboratory, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
- Publication Type:Journal Article
- Keywords:
Acute pancreatitis;
Adhesion of leukocytes to endothelial cells;
Inflammatory responses;
Monoclonal antibody;
Non-human primate;
PSGL-1;
Pancreatic injury;
Therapeutic antibody RH001-6
- From:
Acta Pharmaceutica Sinica B
2023;13(11):4461-4476
- CountryChina
- Language:English
-
Abstract:
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.
