Tumor-specific and Systemic Oncolytic Vaccinia Virus for Novel Cancer Therapy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26640103
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Tottori University
• Principal Investigator: Nakamura Takafumi 鳥取大学, 医学(系)研究科(研究院), 准教授 (70432911)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 癌 / ウイルス療法 / 遺伝子治療 / 抗腫瘍免疫

Outline of Final Research Achievements

Oncolytic viruses are promising therapeutic agents for cancer and are currently under clinical investigation. The virotherapy is novel strategy that viruses infect and replicate within tumor cells, directly lysing and killing them.
In this study, we focus on highly attenuated vaccinia virus which was used for small pox vaccine. However, the vaccinia virus still has property of partial replication in normal cells. Therefore, the vaccinia virus has genetically been engineered in order to not only completely inhibit pathogenic viral replication in normal cells without impairing its therapeutic replication in tumor cells, but also 1) improve viral tumor-homing through regulation of viral morphogenesis and infection and 2) enhance anti-tumor immunity via control of the biological immune response in the tumor microenvironment. Thus, the recombinant oncolytic vaccinia virus achieved tumor-specific and systemic anti-tumor effects in mouse tumor models.

Free Research Field

腫瘍治療学

Academic Significance and Societal Importance of the Research Achievements

現行の治療法に対して極めて高い抵抗性を示し、容易に他臓器に転移する難治性進行癌に対する新規治療法の確立が望まれている。学術的意義は、宿主の免疫を逃れながら血中を介して全身に伝播できるワクシニアウイルス独自の特性を利用し、動物実験においてウイルスの腫瘍集積性の向上を実証したことや、癌免疫療法との併用による抗癌効果の増強に成功したことにある。社会的意義は、癌特異的かつ全身的な効果を併せ持つ癌ウイルス療法の確立を目指した本研究を起点に、本成果が新たながん治療法開発の第一歩となったことにある。