T cell Based Immunotherapies for Cancer
and Chronic Infectious Diseases
ABOUT VIRION THERAPEUTICS
Virion Therapeutics is committed to developing treatments for cancer and chronic infections using targeted novel T cell based immunotherapies that couple a checkpoint blockade with disease-specific antigenic stimulation. Our platform technologies, ChiVax™ and ChiVax-gD™ induce potent and sustained T cell-mediated immune responses against transformed or infected cells and have shown efficacy in a wide range of preclinical animal models including: animal models of fast and slow growing tumors, with viral or human cancer antigens, in young and older animals, and when inserted into failing adenovirus vaccine candidates.
ChiVax-gD utilizes a First-In-Class genetically encoded checkpoint inhibitor of BTLA/CD160-HVEM binding which works early during T cell stimulation to enhance relevant CD8+ T cell responses; given that this checkpoint inhibitor works locally, the risk for serious “off target” side effects is substantially minimized. ChiVax-gD has been shown to produce disease-specific CD8+ T cells that are potent, durable, and more resistant to exhaustion and are broadened to cover sub-dominant epitopes, which could prevent tumor or viral quasi-species escape.
Virion’s lead programs are targeting HPV+ induced cancers and treatment of chronic Hepatitis B Virus (HBV) infection.
Founded in early 2018 to advance technology licensed from The Wistar Institute, an international leader in biomedical research with special expertise in vaccine, cancer and infectious disease research, Virion has built an experienced biotechnology management team, augmented by its advisory board that has extensive domain knowledge in antiviral, vaccine and oncology therapeutic arenas. Virion’s initial development programs are targeted for treatment of human papillomavirus-induced cancers and chronic hepatitis B virus infections.
Background on T cells and Disease
T cells are key to successfully fighting infections and cancers. However, in chronic viral infections or established cancers, T cells can be rendered ineffective by other cell types or become exhausted from prolonged stimulation. Exhaustion, which is characterized by loss of T cell function and increased expression of co-inhibitory markers on the cell surface, has led to the development of new and effective anti-cancer therapies referred to as checkpoint inhibitors. These cancer treatments use monoclonal antibodies to remove the “brakes” placed on the immune system, allowing T cells to re-engage the tumor or infection. The discovery and use of checkpoint inhibitors in the treatment of various cancers has been revolutionary, however, there are limitations: they only work in certain cancer types, are costly to make, require intravenous infusion and are not immune from tumor escape or resistance, often after a short period of time. In addition, since these agents are infused into the bloodstream and therefore go throughout the body, side effects can occur that could be avoided if treatment was directly targeted to infected/cancerous cells.
Chronic Hepatitis B Virus (HBV)
Virion has developed a series of novel vaccine candidates for chronic HBV infection that couple key regions of the HBV virus with our genetically encoded checkpoint inhibitor, gD. Preclinical data have shown these vaccines to produce highly potent and durable HBV-specific T cell responses and when given alone as a single intramuscular injection in preclinical studies, multi-log, sustained HBV viral load reductions. These data are the first immune- or T cell-based treatments to show such results (see more) and are consistent with gD’s mechanism of action which broadens and enhances T cell recognition to include sub-dominant epitopes, which are more resistant to exhaustion. VRON-0200 could be a foundational component of multi-modal therapies for HBV functional cure.
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SCIENTIFIC PUBLICATIONS AND PRESENTATIONS
Zhang Y and Ertl CJ (2014). The Effect of Adjuvanting Cancer Vaccines with Herpes Simplex Virus Glycoprotein D on Melanoma-Driven CD8+ T Cell Exhaustion. J. Immunol. 193(4): 1836-46.
Lassaro MO, et al. (2011). Active Immunotherapy Combined With Blockade of a Coinhibitory Pathway Achieves Regression of Large Tumor Masses in Cancer-prone Mice. Mol. Ther. 19(9):1727-36.
Diniz MO, et al. (2010). Immune Responses and Therapeutic Antitumor Effects of an Experimental DNA Vaccine Encoding Human Papillomavirus Type 16 Oncoproteins Genetically Fused to Herpesvirus Glycoprotein D. Clin. Vaccine Immunol. 17(10): 1576-83.
DiMenna L, et al. (2010). Augmentation of Primary Influenza A Virus-Specific CD8+ T Cell Responses in Aged Mice through Blockade of an Immunoinhibitory Pathway. J. Immunol. 184: 5475-5484).
Chen H, et al. (2010). Adenovirus-Based Vaccines: Comparison of Vectors from Three Species of Adenoviridae. J. Virol. 84(20): 10522-32.
Lassaro MO, et al. (2008). Targeting of antigen to the herpesvirus entry mediator augments primary adaptive immune responses. Nat. Med. 14(2): 205-212.
Reyes-Sandoval A, et al. (2004). Human Immunodeficiency Virus Type 1-Specific Immune Responses in Primates upon Sequential Immunization with Adenoviral Vaccine Carriers of Human and Simian Serotypes. J. Virol. 78(14): 7392-7399.