Takafumi Nakamura,
Associate Professor, Division of Molecular Medicine,
Tottori University
Dr. Nakamura received his PhD from Tottori University, Japan under the supervision of Professor Kenzo Sato in 2001. He then joined Professor Stephen J. Russell laboratory in molecular medicine program at Mayo Clinic, Rochester, MN, USA as a postdoctoral research fellow (2002 – 2004) and research associate (2004 – 2005). He worked as Sakigake Researcher (2006 – 2010) and Project Associate Professor (2009 – 2012) at The University of Tokyo, Japan. In 2012, he was appointed as an associate professor in the Division of Molecular Medicine, Department of Biomedical Science, Graduate School of Medical Sciences, Tottori University, Japan. His research interests include 1) oncolytic virotherapy, 2) cancer gene therapy, 3) cancer immunotherapy, 4) viral entry and fusion for infection, and 5) tumor biology. He has published over 50 articles including major academic journals such as Nature Biotechnology, Science Translational Medicine, Cancer Research, Clinical Cancer Research, Molecular Therapy, Molecular Therapy Oncolytics, Human Gene Therapy, and Journal of Virology and has registered over 15 patents. Recently, he has been focusing on translating his next-generation oncolytic vaccinia virus pipelines into clinic.
Oncolytic Vaccinia Vectors for Cancer Immunotherapy
Thursday, 6 October 2022 at 17:00
Add to Calendar ▼2022-10-06 17:00:002022-10-06 18:00:00Europe/LondonOncolytic Vaccinia Vectors for Cancer ImmunotherapyLab-on-a-Chip and Microfluidics Asia 2022 in Tokyo, JapanTokyo, JapanSELECTBIOenquiries@selectbiosciences.com
Vaccinia virus, once widely used for smallpox vaccine, has been genetically engineered and used as an oncolytic virus for cancer virotherapy. The therapeutic index is successfully enhanced by stricter tumor-specific viral replication, stronger oncolytic potency, and optimized induction of antitumor immunity. Two viral proteins VGF and O1 contribute to viral replication and spread by activation of EGFR-dependent MAPK/ERK pathway. VGF- and O1-deleted vaccinia virus (MDRVV) inhibited pathogenic viral replication in normal cells without impairing therapeutic replication in tumor cells. Recently, fusogenic vaccinia virus (FUVAC) was discovered during plaque purification of the MDRVV. FUVAC has a nonsense mutation in the viral gene K2L, whereas other viral genomes are maintained in the MDRVV. Using a bilaterally tumor-bearing syngeneic mouse model, unilateral administration of FUVAC more efficiently enhanced CD8+ T cell infiltration and inhibited tumor growth in not only treated tumors but also untreated tumors than MDRVV. Interestingly, FUVAC reduced tumor-associated immune suppressive cells such as regulatory T cells, myeloid-derived suppressor cells and tumor-associated macrophages in the injected tumor. In accordance with the change for the better, the anticancer effects of FUVAC in both injected and non-injected tumors were completely suppressed by depletion of CD8+ T cells. Taken together, fusogenic vaccinia virus exerts more potent antitumor immune responses by modulating the tumor microenvironment than non-fusogenic vaccinia virus. Furthermore, the simultaneous expression of immune-modulating genes in FUVAC augmented the antitumor activity via inducing potent and durable antitumor immune responses following viral oncolysis. The combined properties have the potential to overcome oncolytic virus-resistant tumors which limit the clinical benefits due to tumor heterogeneity and the complexity of tumor microenvironment. Thus, FUVAC would be better therapeutic platform as a next-generation oncolytic vaccinia vector.
Add to Calendar ▼2022-10-06 00:00:002022-10-07 00:00:00Europe/LondonLab-on-a-Chip and Microfluidics Asia 2022Lab-on-a-Chip and Microfluidics Asia 2022 in Tokyo, JapanTokyo, JapanSELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2022-10-06 17:00:002022-10-06 18:00:00Europe/LondonOncolytic Vaccinia Vectors for Cancer ImmunotherapyLab-on-a-Chip and Microfluidics Asia 2022 in Tokyo, JapanTokyo, JapanSELECTBIOenquiries@selectbiosciences.com
