2021 Fiscal Year Final Research Report
the superiority of the p53 overexpressing oncolytic adenovirus mediated tumor-specific to chemotherapies in immunotherapy for a pancreatic cancer
| Project/Area Number |
20K17690
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Okayama University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | ウイルス療法 / 膵癌 / 免疫療法 / 腫瘍融解アデノウイルス / p53 |
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| Outline of Final Research Achievements |
Pancreatic cancer is aggressive cancer with an immunologically “cold” microenvironment. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702). Here, we investigated the immunological efficacy of OBP-702 for pancreatic cancer. Activation of CD8+ T cells by OBP-702 was retained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN+OBP-702 showed significant anti-tumor effects and increased CD8+ T cells in OBP-702-un-injected tumors. Finally, GN+OBP-702 sustained long-term anti-tumor effects in a neoadjuvant model even after tumor resection. In conclusion, OBP-702 can be a long-term immunostimulant which brings sustained anti-tumor effects on immunologically cold pancreatic cancer.
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| Free Research Field |
腫瘍融解ウイルス
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果はp53を誘導する腫瘍融解アデノウィルス製剤が既存化学療法薬剤より免疫を誘導し，併用療法においても薬剤の相乗効果のみならず免疫学的効果を発揮することをマウスモデルで示した．遠隔転移モデル，術前治療モデルそれぞれで有効な結果がでたため，難治性癌である膵癌の幅広い患者様に対する新規治療として，OBP-702を使用したウイルス療法の重要な前臨床データを作ることができた．また免疫チェックポイント阻害薬との併用効果が期待されるデータもでたため，今後膵癌の免疫療法応用にもつながるプロジェクトとなった．
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