强干扰素诱导病毒载体与低剂量 Nivolumab 加 Ipilimumab 的顺序组合可提供慢性乙型肝炎病毒感染的功能性治疗：提出新模式的技术报告
Tibor Bakacs 1 , Rifaat Safadi 2 , László G Puskás 3 , Liliána Z Fehér 3 , Imre Kovesdi 4
隶属关系
隶属关系
Sequential Combination of a Strong Interferon Inducer Viral Vector With Low Doses of Nivolumab Plus Ipilimumab Could Provide Functional Cure in Chronic Hepatitis B Virus infections: Technical Report Proposing a New Modality
Tibor Bakacs 1 , Rifaat Safadi 2 , László G Puskás 3 , Liliána Z Fehér 3 , Imre Kovesdi 4
Affiliations
Affiliations
1
Department of Probability, Alfred Renyi Institute of Mathematics, The Eotvos Lorand Research Network (ELKH), Budapest, HUN.
2
The Liver Unit, Hadassah Medical Organization, Hadassah Hebrew University Medical Center, Jerusalem, ISR.
3
Drug Development, AVIDIN Ltd., Szeged, HUN.
4
Virology, ImiGene, Inc., Rockville, USA.
Based on the recommendation of the International Coalition to Eliminate hepatitis B virus (ICE-HBV), we intend to mimic the spontaneous resolution of HBV infection to achieve a functional cure of chronic hepatitis B virus (HBV) infection. To this end, we propose sequential targeting of the innate and adaptive host immune responses. Long-term suppression of HBV replication and hepatitis B surface antigen (HbsAg) production will be achieved first by inducing a strong innate immune response. The clinically validated viral superinfection therapy (SIT) will be administered, which employs an attenuated, non-lytic, double-stranded RNA (dsRNA) infectious bursal disease virus (IBDV) that provides an exceptionally strong interferon (IFN) response. Then, the exhausted HBV-specific T cell function will be restored by blocking the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) receptors with immune checkpoint inhibitors (ICIs). In order to minimize any risk of toxicity, off-label low doses of nivolumab (0.5 mg/kg) plus ipilimumab (0.3 mg/kg) will be administered, the safety and efficacy of which has already been demonstrated in 131 unselected stage IV cancer patients. We predict that this combination therapy will provide sustained off-treatment virological and clinical responses during a relatively short treatment period.