Development of modified oncolytic virus targeting refractory relapsed ovarian tumor

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09751
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Nagoya University
• Principal Investigator: Nawa Akihiro 名古屋大学, 医学系研究科, 特任教授 (90242859)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腫瘍溶解性ウイルス / 卵巣癌 / 抗癌剤 / 葉酸受容体 / インドキシル硫酸

Outline of Final Research Achievements

Since recurrent ovarian cancers is often resistant to chemotherapy, there is a need for an alternative treatment to chemotherapy. Oncolytic virus (OV) therapy has been reported to have excellent therapeutic effects with local inoculation for various solid tumors. In peritoneal dissemination of ovarian cancer, it is difficult to inoculate each disseminated lesion individually, so intraperitoneal inoculation of OV targeting ovarian cancer cells is desirable, but no therapeutic target has been identified for ovarian cancer. Using the fluorescent dye FITC as an adapter, we attempted to create an improved OV (FOV) that can target various molecules without the intervention of gene modification. In addition to examining the usefulness of folic acid receptor α as a therapeutic target for ovarian cancer, we also investigated the possibility that ovarian cancer may be exacerbated by anticancer drugs.

Free Research Field

産婦人科

Academic Significance and Societal Importance of the Research Achievements

FRα標的薬である葉酸シクロデキストリンは、FRαだけでなく、プロトン依存性葉酸トランスポーター（PCFT）も標的化することが示唆された。ヒトPCFTは小腸や肝臓などでも発現すると報告されており、FRα標的薬はこれらの臓器を標的化してしまう可能性が考えられた。他方、シスプラチンはマウスに急性腎障害を引き起こし、血中にインドキシル硫酸（IS）を蓄積させること、IS投与マウスにおいては卵巣癌の増殖および転移が促進されることが示唆された。ISは芳香族炭化水素受容体（AhR）を介して卵巣癌細胞のシグナル伝達を異常制御しており、AhRを阻害することで抗癌剤による卵巣癌の増悪を抑制できる可能性がある。