Development of a combination cancer therapy utilizing oncolytic adenovirus with chemotherapy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K20381
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Hokkaido University
• Principal Investigator: Matsuda Aya 北海道大学, 歯学研究院, 特別研究員(RPD) (60514312)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 腫瘍溶解ウイルス / 口腔がん / 抗がん剤

Outline of Final Research Achievements

Oncolytic adenovirus is an attractive tool for cancer therapy. We developed a novel oncolytic adenovirus ( AdΔE4) based on the ARE-mRNA stabilization system. In this study, we examined the combination effect of AdΔE4 with cisplatin (CDDP). In the case of combined use of AdΔE4 with CDDP, the cell survival rate of CDDP resistant cancer cells were very lower compared with those of single treatments. These results indicate that new virus available for the combination cancer therapy with CDDP. To evaluate the mechanism of the combination effect of AdΔE4 with CDDP, we treated cancer cells by CDDP. CDDP treatment of cancer cells resulted in higher expression of HuR protein in the cytoplasm of cancer cells. These results suggest that the HuR　mediated ARE-mRNA stabilization system plays an important role in AdΔE4 replication.

Free Research Field

口腔病理

Academic Significance and Societal Importance of the Research Achievements

がんが抗癌剤に対して抵抗性を示すことがあり、臨床上大きな問題になっている。我々は抗癌剤耐性を克服できる方法を探るため研究を行い、CDDPと腫瘍溶解ウイルス（AdΔE4）の併用はCDDP耐性腫瘍に効果があることを見出した。このことからCDDPとAdΔE4の併用療法はこれまで治療法がなかったがんの新しい治療法となる可能性があり、社会的な意義があると考える。