2022 Fiscal Year Final Research Report

Combination therapy of molecular targeted drugs and gene therapy for invasive brain tumors and elucidation of the tumor microenvironment

Research Project

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Project/Area Number	20K09325
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56010:Neurosurgery-related
Research Institution	Hamamatsu University School of Medicine
Principal Investigator	Kazuhiko Kurozumi 浜松医科大学, 医学部, 教授 (20509608)
Co-Investigator(Kenkyū-buntansha)	藤井謙太郎岡山大学, 医歯薬学総合研究科, 助教 (40799318) 安原隆雄岡山大学, 医歯薬学総合研究科, 准教授 (50457214) 島津洋介岡山大学, 医学部, 客員研究員 (90854084)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	分子標的薬 / 遺伝子治療 / 悪性脳腫瘍 / 腫瘍溶解ウイルス / アデノウイルス
Outline of Final Research Achievements	Malignant brain tumors are an extremely poor prognosis, and Gene therapy and molecular-targeted drugs are promising treatments. In this study, we investigated the combination therapy of molecular-targeted drugs and gene therapy for invasive brain tumors and the involvement of tumor microenvironment-related factors such as the CCN family. In a collaborative study with Okayama University, we focused on tumor microenvironment-related factors such as the CCN family. We found that differentiated glioma cells (DGCs) accelerate tumor progression by making the tumor microenvironment via CCN1-mediated macrophage infiltration. Moreover, we performed TK/GCV suicide gene cell therapy using deciduous tooth pulp stem cells (SHED) and confirmed tumor tropism and antitumor effect. In addition, preliminary OV experiments are underway for oncolytic virus (OV) experiments. In the future, we plan to perform combination therapy.
Free Research Field	Brain tumor
Academic Significance and Societal Importance of the Research Achievements	浸潤性脳腫瘍に対する分子標的薬と遺伝子治療との併用療法とCCNファミリーなどの腫瘍微小環境関連因子の関与については再現性のある結果がえられた。腫瘍微小環境の変化を理解することは腫瘍進展のメカニズムを解明することとなる。また、脱落乳歯歯髄幹細胞（SHED）を用いたTK/GCV自殺遺伝子細胞治療、腫瘍溶解ウイルス療法、分子標的薬と遺伝子治療との併用において、新たな治療法が確立されれば、世界的にもbreakthrough となる悪性脳腫瘍の研究となる。