Combination of HBV Immunotherapy with shRNA - Mediated PD-1/PDL Checkpoint Inhibition for Treatment of Chronic HBV
Abstract
More than 400 million people worldwide are chronically infected with the hepatitis B virus (HBV). Estimates of the chronic hepatitis B (CHB) prevalence in the US range from 850,000 to 2.2 million people. CHB often progresses to cirrhosis, liver failure, and hepatocellular carcinoma (HCC). The existing antiviral drugs for treatment of HBV are not curative and require life-long treatment, which results in viral resistance. Therefore, new therapeutic approaches for the treatment of chronic HBV are sorely needed for this high prevalent disease. The main goal of this project is to improve immunogenicity and efficacy of the candidate immunotherapeutic vector CARG-301 using virus-like vesicle (VLV) platform for delivery of 3 HBV antigens and suppression of immune checkpoint PD-L1. After testing the efficacy of the CARG-301-based immunotherapy in a preclinical model of CHB, we will develop the cGMP manufacturing process and initiate IND-enabling studies to prepare CARG-301 for clinical trials. If our approach is successful, a treatment regimen of CARG-301 could overcome immune tolerance in CHB subjects with high viral load and antigenemia, prevent disease progression, and would improve quality of life of CHB patients while having a profound clinical and healthcare implications.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1208686
Entities
People
- Valerian Nakaar
Organizations
- Albany Medical College
- Yale University