HBsAg and TLR7/8 dual-targeting antibody-drug conjugates induce sustained anti-HBV activity in AAV/HBV mice: a preliminary study
簡介:
- 作者: Xinya Ye, Xiaoqing Chen, Han Liu, Yichao Jiang, Chengyu Yang, Tao Xu, Ziyou Chen, Yalin Wang, Fentian Chen, Xue Liu, Hai Yu, Quan Yuan, Ningshao Xia, Yuanzhi Chen, Wenxin Luo
- 雜志: Antibody Therapeutics
- Doi: https://www.doi.org/10.1093/abt/tbae016
- 出版日期: 2024 Jul 3
論文中使用的產品/服務
Quotation shows PackGene:The adeno-associated virus (AAV)-HBV1.3, encapsulating 1.3 copies of the HBV genome (genotype B, serotype adw) in AAV serotype 8 capsids, was acquired from PackGene Biotech (Guangzhou, China).
Research Field:anti-HBV activity
AAV Serotype:AAV8
Targeted organ:liver
Animal or cell line strain:mice
摘要
Hepatitis B virus (HBV) infection is a significant global health concern due to elevated immunosuppressive viral antigen levels, the host immune system’s inability to manage HBV, and the liver’s immunosuppressive conditions. While immunotherapies utilizing broadly reactive HBV neutralizing antibodies present potential due to their antiviral capabilities and Fc-dependent vaccinal effects, they necessitate prolonged and frequent dosing to achieve optimal therapeutic outcomes. Toll-like receptor 7/8 (TLR7/8) agonists have been demonstrated promise for the cure of chronic hepatitis B, but their systemic use often leads to intense side effects. In this study, we introduced immune-stimulating antibody conjugates which consist of TLR7/8 agonists 1-[[4-(aminomethyl)phenyl]methyl]-2-butyl-imidazo[4,5-c]quinolin-4-amine (IMDQ) linked to an anti-hepatitis B surface antigen (HBsAg) antibody 129G1, and designated as 129G1-IMDQ. Our preliminary study highlights that 129G1-IMDQ can prompt robust and sustained anti-HBsAg specific reactions with short-term administration. This underscores the conjugate’s potential as an effective strategy for HBsAg clearance and seroconversion, offering a fresh perspective for a practical therapeutic approach in the functional cure of CHB.
關于派真
作為一家專注于AAV 技術十余年,深耕基因治療領域的CRO&CDMO,派真生物可提供從載體設計、構建到 AAV、慢病毒和 mRNA 服務的一站式解決方案。憑借深厚的技術實力、卓越的運營管理和高標準的服務交付,我們為全球客戶提供一站式CMC解決方案,包括從早期概念驗證、成藥性評估到IIT、IND及BLA的各個階段。
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憑借我們獨立知識產權的π-alphaTM 293 細胞AAV高產技術平臺,我們能將AAV產量提高多至10倍,每批次產量可達1×101?vg,以滿足多樣化的商業化和臨床項目需求。此外,我們定制化的mRNA和脂質納米顆粒(LNP)產品及服務覆蓋藥物和疫苗開發的各個階段,從研發到符合GMP的生產,提供端到端的一站式解決方案。