Development of monoclonal antibodies against PD-L1 and preliminary investigation on potential application in treatment of chronic hepatitis B virus in-fection
10.3969/j.issn.1000-484X.2016.07.016
- VernacularTitle:抗PD-L1单抗的研制及其对乙型肝炎病毒的抑制效果初步研究
- Author:
Yong WU
;
Tianying ZHANG
;
Liuwei SONG
;
Ningshao XIA
;
Quan YUAN
- Publication Type:Journal Article
- Keywords:
PD-L1;
Therapeutic monoclonal antibodies;
HBV;
Immunotherapy
- From:
Chinese Journal of Immunology
2016;32(7):1004-1008,1012
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To get specific monoclonal antibodies ( mAbs) against PD-L1 which can block PD-1/PD-L1 binding, and explore the feasibility of its application on the treatment of chronic HBV infection preliminarily by in vitro and in vivo model. Methods:E. coli expression and series chromatography purification system were employed to get human and mouse PD-1/PD-L1 that had binding activity in vitro. By immunizing BALB/c mouse with purified recombination proteins of PD-L1,mAb hybridoma cell lines against PD-L1 were obtained. The reactivity with human/mice PD-L1 of individual antibody and the interaction blocking activity of the mAbs to PD-1/PD-L1 in vitro were examined by indirect chemiluminescence immune assay. Results: 8 cell lines against PD-L1 were obtained and 2 Anti-PDL1 mAbs (Ab5 &Ab6) performed strong immune activity to human/mice PD-L1 and blocking activity to PD-1/PD-L1. In the PBMC stimulation experiment of chronic HBV patient,Ab5 and Ab6 could promote theγ-IFN levels. With HBV in-fecting mice model,intravenous injections of these mAbs induced dramatically decrease of HBV DNA copies about 20 times, HBsAg levels in serum reduced to 30% of the baseline level. Conclusion:We obtained 2 PD-L1 mAbs with the reactivity to human/mice PD-L1 and blocking activity to PD-1/PD-L1. The 2 mAbs can promote T cell function in PBMC stimulation culture of chronic HBV patient, have significant antiviral effect in HBV transgenic mice and can be candidates for immunotherapy applications.
