Cell death mechanisms induced by infection with oncolytic measles virus

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07291
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Fujiyuki Tomoko 東京大学, 生産技術研究所, 特任准教授 (50610630)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 麻疹ウイルス / 癌治療 / Nectin-4 / 細胞死

Outline of Final Research Achievements

Oncolytic viruses (OV) is a rising tools for cancer therapy, because OV infects and replicates in cancer cells to kill. However, molecular and cellular mechanisms by which OV exerts anti-tumor effect remain to be clarified. An oncolytic recombinant measles virus (rMV-SLAMblind) which we have developed infects and kills cancer cells. To understand cell death mechanism induced by rMV-SLAMblind infection, modes of cell death were analyzed. Several cancer cell lines were infected with rMV-SLAMblind, and activation of molecular markers of cell death were tested. Whereas it was believed that measles virus infection causes apoptosis, these cells showed activation of non-apoptosis marker molecules. In addition, induction of cytokine production was detected after rMV-SLAMblind infection. These results suggest that rMV-SLAMblind infection to cancer cells induces immunogenic cell death, which may contribute to establish anti-tumor immunity.

Free Research Field

ウイルス学

Academic Significance and Societal Importance of the Research Achievements

Oncolytic virus (OV) は癌細胞に感染して増殖することで癌細胞を殺傷することから、次世代癌治療ツールとして開発が進められているが、OVが抗腫瘍効果を発揮する機序については不明な点が多い。我々が開発した癌治療用組換え麻疹ウイルス(rMV-SLAMblind)は、癌細胞に感染して直接殺傷するだけでなく、抗腫瘍免疫を誘導する可能性があり、ウイルス感染後の細胞死様式が治療時の免疫応答に影響すると推測される。本研究の成果は、rMV-SLAMblind療法による免疫誘導のメカニズムを解く端緒となり、ウイルス療法のさらなる改良のヒントも与えるものである。