A novel oncolytic virus therapy targeting tumor microenvironment of diffuse midline glioma

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20792
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Okayama University
• Principal Investigator: Tomita Yusuke 岡山大学, 医学部, 客員研究員 (90963033)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: びまん性正中神経膠腫 / 変異ヒストン蛋白 / 脳オルガノイド / 腫瘍溶解ヘルペスウイルス

Outline of Final Research Achievements

We could stably maintain the murine diffuse midline glioma (DMG) cell lines that had H3.3K27M mutation in vitro. DMG cells mainly proliferated to form spheroid cell clusters, but some DMG cell lines easily differentiated to the adhesive cells. H3.3K27M mutant protein was indirectly confirmed with Green Fluorescent Protein (GFP) tagged to H3.3K27M structure. Also, H3.3K27M sequence was validated by Sanger sequencing. We could induced differentiation from the murine embryonal stem cells to brainstem organoid under the specific conditions. Co-culture with DMG cells and brainstem organoid made DMG cells more proliferative around the organoid. Oncolytic herpes virus had the cytotoxic effect in vitro against the DMG cells.

Free Research Field

脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

DMGは放射線療法が一時的な効果を示すのみで現時点で有効な治療法がない難治性の腫瘍である。DMGの治療が難しい理由として摘出が難しいこと、血液脳関門があり薬剤が腫瘍に到達できないことが挙げられる。腫瘍溶解ヘルペスウイルスは腫瘍内投与することで腫瘍細胞でのみ増幅して細胞障害性を示すことができる特徴がある。今回の実験で試験管内におけるDMGへの有効性は確認ができた。今後、さらに共培養条件下において腫瘍溶解ウイルスの有効性を確認し、さらに有効性を向上させる併用治療の開発ができれば臨床応用に向けて大きく先進すると期待される。