Combination of HBV Immunotherapy with shRNA-Mediated PD-1/PDL Checkpoint Inhibition for Treatment of Chronic HBV
Abstract
Background: Approximately 400 million people worldwide are chronically infected with the hepatitis B virus (HBV) and approximately 30 percent of the global population has been exposed to HBV, making it one of the most common viral infections in the world. In the United States alone, up to 2.2 million people live with continual or chronic HBV (CHB), many of whom are unaware of their infection. The immune system often naturally eliminates HBV after exposure and initial infection. However, if the immune system does not clear the infection, the body becomes tolerant and no longer sees HBV as an enemy to eliminate. Over time, HBV infection leads to progressive worsening of liver function, inflammation, and increased risk of cirrhosis, liver failure, and hepatocellular carcinoma. While there are existing antiviral drugs for the treatment of CHB, they are expensive and do not eliminate the infection. Moreover, the virus develops resistance to the current drugs over time, rendering the treatment ineffective. Therefore, new therapeutic approaches for the treatment of CHB are sorely needed for this highly prevalent disease. This project is designed to perform an initial clinical study with an RNA therapeutic vaccine for patients who are infected with HBV and present with mild HBV disease. The investigational drug is designed to re-train the patient’s immune system to attack and eliminate the virus. Relevance to Topic Area: Hepatitis B is one of the topic areas of interest to the Peer Reviewed Medical Research Program. The specific area addressed by this proposal is, Basic/translational research leading to new therapies for viral hepatitis and hepatocellular carcinoma. The proposed study aims to improve efficacy of an RNA therapeutic vaccine for infected patients who are on existing standard therapies. This project will use an animal model of viral hepatitis to demonstrate efficacy of the best candidate and develop the manufacturing process to prepare for clinical studies. Ultimate Applicability and Impact of the Research: This new class of therapeutic vaccines can ultimately be used to safely treat patients with different degrees of HBV disease (early to late stage) either as a stand-alone treatment or in combination with existing drugs. Short-Term Impact: This project will test the efficacy of a new RNA immunotherapy for the treatment of CHB. The expected outcome of this study is to demonstrate efficacy to support the expansion of vaccine testing in clinical settings. Lastly, this therapy is the next phase of development for the novel RNA immunotherapy platform. Thus, the efficacy data will enable testing of other product candidates in development by the sponsor. If successful, the first-in-class therapeutic vaccine could lead to expedited and cost-effective treatment of CHB as well as decreased mortality of United States military Service Members and Veterans and their dependents. Long-Term Impact: This proposal will make important progress toward the development of a potentially curative treatment of a prevalent disease that causes significant health impact. This would be a paradigm shift for the treatment of this disease. After completing the current study, CaroGen will be well positioned to initiate clinical trials, secure corporate partnerships, raise venture capital, and pursue an initial public offering on the capital markets in order to accelerate product development and commercialize its much-needed products.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210762
Entities
People
- Valerian Nakaar
Organizations
- United States Army