Yasufumi Kaneda's Biography

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Virotherapy, Cell-based Therapy and Gene Therapy with Non-Replicating Oncolytic Virus Particle (HVJ-E/GEN0101) for the Treatment of Cancers

Tuesday, 12 November 2019 at 09:10

Add to Calendar ▼2019-11-12 09:10:002019-11-12 10:10:00Europe/LondonVirotherapy, Cell-based Therapy and Gene Therapy with Non-Replicating Oncolytic Virus Particle (HVJ-E/GEN0101) for the Treatment of CancersCell and Gene Therapy Asia 2019 in Kobe, JapanKobe, JapanSELECTBIOenquiries@selectbiosciences.com

HVJ-E/GEN0101 is an inactivated virus particle derived from murine parainfluenza virus HVJ (Hemagglutinating virus of Japan). It has been originally developed as a vector for gene therapy. We discovered the virus particle itself has an activity to induce cancer-cell specific apoptosis and necroptosis. It also induces innate and adaptive immunities necessary to attack cancer cells. The active ingredient is a single strand RNA fragment derived from genomic RNA of the virus. It binds to an intracellular nucleic acid receptor RIG-I and induces expressions of cytokines, chemokines and apoptosis-related genes in vitro and in vivo. We conduced safety studies using Cynomolgus monkeys and started investigator initiated clinical studies in Osaka University to develop HVJ-E as a new drug for cancer immune- and viro-therapies. To date five phase I or I/IIa investigator initiated clinical studies has been finished. The targets cancers are melanoma, prostate cancer and malignant pleural mesothelioma. In these studies, the safety, efficacy and mechanism of actions of the drug have been evaluated. No serious adverse event related to the drug was observed and safety of the drug is confirmed in clinical. Reduction and eradication of tumor lesions were observed in a dose dependent manner. Induction of innate and adaptive immunities after administration of HVJ-E was observed in clinical, suggesting that the efficacy is mediated by immune reactions. The efficacy is expected to be increased in combination with anti-PD-1 antibody therapy, we are now conducting two phase II studies of melanoma and malignant pleural mesothelioma for the evaluation of efficacy of combinational therapy.

In addition to cancer virotherapies, we are also conducting cell therapy and gene therapy of HVJ-E for the treatment of ovary and breast cancers, respectively. In the cell therapy, we prepare hybrid cells of dendritic cell (DC) and irradiated cancer cells derived from patients. HVJ-E is used for cell fusion, maturation of DC and induction of cancer immunities. Cancer antigens are directly captured by DC via membrane fusion between DC and irradiated cancer cells, and DC efficiently presents antigens to helper T cells. In the gene therapy, we use plasmid DNA expressing chemokine gene (CXCL2) to recruit neutrophils into tumor bed. Intratumoral injection of HVJ-E improve a tumor microenvironment by the induction of Type I neutrophils which suppress the growth of tumor.

To establish sustainable cycle (or system) to create innovative drugs in Osaka University, we are trying to bridge basic scientists, clinicians and researchers of companies. Osaka University applys and maintains patents of the seed of drugs in collaboration with companies as applicant to obtain appropriate royalty. Basic scientists and clinicians designed their investigator initiated clinical studies in collaboration, since custom-made design based on scientific data is necessary to develop innovative drugs. We also bridged academia and industries to conduct our phase II investigator initiated clinical studies. We are now trying to make collaboration scheme with pharmaceutical companies to complete sustainable cycle.