iPS cells producing retroviral replicating vector for malignant glioma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03046
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Keio University
• Principal Investigator: toda masahiro 慶應義塾大学, 医学部(信濃町), 教授 (20217508)
• Co-Investigator(Kenkyū-buntansha): 植田 良 慶應義塾大学, 医学部(信濃町), 講師 (30317143)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Glioma / iPS / Neural stem cell / Viral vector / Suicide gene / Genome editing

Outline of Final Research Achievements

Glioblastoma is characterized by diffuse infiltration into the normal brain. Invasive glioma stem cells (GSCs) are an underlying cause of treatment failure. New therapeutic approach targeting invasive GSCs is required. In this study, we showed that human iPS cell-derived neural stem cells (NSCs) could efficiently produce viral vector. Optimal culture condition of viral vector -producing NSCs was found. Infection rate was quantitatively evaluated in vitro. Furthermore, three-dimensional images of brain clearing revealed that NSCs trafficked to the GSCs and produced viral vector covered the broad area of invasive GSCs. Finally, our established NSCs showed antitumor effects in GSC mouse models, leading to the prolonged survival. Our results indicate the potential benefit of viral vector-producing NSCs for invasive GSCs. Furthermore, the present research concept may become a platform to promote clinical studies using human iPS cell.

Free Research Field

脳神経外科

Academic Significance and Societal Importance of the Research Achievements

本研究により樹立される治療用NSCは、グリオーマの浸潤性を克服する新たな治療戦略となり、グリオーマの生命予後の改善につながる可能性がある。またグリオーマで治療成績を残すことが出来た際には、その他の膵癌をはじめとする悪性・難治性腫瘍にも応用可能であり汎用性も高く社会的意義も大きい。この研究開発はiPS細胞を再生医療以外の疾患(がん)治療に応用する極めて革新的な1st clinical trial となり得るプロジェクトと言える。