Oncorus is developing potent oncolytic immunotherapies for cancer.
Oncorus oHSV is controlled by certain micro-RNAs (miRNAs) that are present in healthy cells, but absent in cancer cells. Typically, miRNAs regulate the ability of classical messenger RNA (mRNAs) to be translated into protein or promote the degradation of mRNAs. By engineering miRNA binding sites into essential viral genes, oHSV replication and cellular destruction is prevented in healthy cells. Since cancer cells lack these specific miRNAs, Oncorus oHSV is free to replicate in and destroy them.
How does it work?
- ONCR-001, our lead candidate, will be injected directly into a patient’s tumor. Upon replication, it will directly kill tumor cells and will release multiple tumor antigens that will trigger an immune response.
- As a consequence, oncolytic vector therapy can be defined as the “ultimate” personalized medicine as each patient will develop an immune response against their own specific tumor antigens.
- The Oncorus approach is based on HSV vectors that retain all viral functions. The safety is ensured by (i) selective infection through tumor-specific receptors and (ii) selective replication based on differential expression of microRNAs (miRs) in tumor and normal cells.
- Given the large available genetic space within Oncorus’s oHSV, our second generation viruses will contain potent therapeutic payloads designed to enhance the therapeutic potential against a wide variety of tumor types
What’s inside Oncorus oHSV?
- Mazzacurati et al., Use of miRNA Response Sequences to Block Off-target Replication and Increase the Safety of an Unattenuated, Glioblastoma-targeted Oncolytic HSV, Mol Ther, 2015.
- Uchida et al., Novel Mutations in gB and gH Circumvent the Requirement for Known gD Receptors in Herpes Simplex Virus 1 Entry and Cell-to-Cell Spread, J Virol, 2013.
- Uchida et al., Effective Treatment of an Orthotopic Xenograft Model of Human Glioblastoma Using an EGFR-retargeted Oncolytic Herpes Simplex Virus, Mol Ther, 2013.
- Grandi et al., Design and application of oncolytic HSV vectors for glioblastoma therapy, Expert Rev Neurother, 2009.