Gene therapy for a novel diffuse intrinsic pontine glioma model initiated in Olig2-expressing progenitors

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17931
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Okayama University
• Principal Investigator: Shimazu Yosuke 岡山大学, 医学部, 客員研究員 (90854084)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Ad-SGE-REIC / びまん性橋膠腫モデル

Outline of Final Research Achievements

We injected malignant glioma cell lines stereotactically into the brainstem to generate a mouse brain tumor model using U87ΔEGFR, a human malignant glioma cell line, and GL261, a mouse malignant glioma cell line. Regarding the Ad-REIC toxicity test, Ad-REIC was administered to the brainstem of immunodeficient mice (Balbc nu/nu) and immunocompetent mice (C57BL6). The dose of virus was initially 2.0x10^7 pfu, then increased to 2.0x10^8 pfu, and the mice were observed for 1 week. No obvious changes were observed in mice and these doses were considered non-toxic. Regarding experiments using Ad-SGE-REIC, we conducted basic experiments on the combination of Ad-SGE-REIC and bevacizumab in our laboratory, and a paper on those results were published. In addition, a paper on research related to a diffuse pontine glioma model initiated in Olig2-expressing progenitors, which was conducted by the primary researcher in the United States, was published.

Free Research Field

脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

細胞特異的遺伝子導入システムであるRCAS/Tv-aシステムを用いた動物モデルは、発生機序など真のヒトびまん性橋膠腫（DIPG）に近い性質を有している。RCAS/Tv-aシステムで作成したマウスモデルでは、免疫能が正常であることも特徴の一つである。一方、Ad-REICを用いた遺伝子治療は、悪性神経膠腫に対して臨床試験が開始されたばかりで、将来性がある治療である。本研究は、細胞特異的遺伝子導入システムにより作成されたマウスDIPGモデルを用いることでさらにヒトDIPGの理解を深め、Ad-SGE-REICに関する基礎研究の成果は、今後の臨床応用に生かされると考えている。