| Project/Area Number |
17K18252
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Digestive surgery
Gastroenterology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
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| Research Collaborator |
TODO Tomoki
KAIBORI Masaki
MATSUSHIMA Hideyuki
OKUMURA Tadayoshi
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 肝細胞癌 / 第三世代制限増殖型遺伝子組換えHSV－1 / G47Δ / IL-12 / 可溶型B7-1 / 抗腫瘍免疫 / 免疫チェックポイント阻害薬 / ウイルス療法 / ソラフェニブ |
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| Outline of Final Research Achievements |
Multimodality therapies are used to manage patients with hepatocellular carcinoma (HCC), although advanced HCC is incurable. Oncolytic virus therapy is probably the next major breakthrough in cancer treatment. The third-generation oncolytic herpes simplex virus type 1 (oHSV-1) G47Δ and T-01 kill tumor cells without damaging the surrounding normal tissues. “Arming” oHSV with transgene(s) is a useful strategy to add certain antitumor functions to oncolytic viruses. T-01 is an base oHSV for “arming” interleukin (IL)-12 or soluble B7-1. “Arming” IL-12 or soluble B7-1 oHSV may significantly enhance the antitumor efficacy via augmentation of the antitumor immunity induction. At current study, we investigated the antitumor efficacy of “arming” oHSV on HCC and the host’s immune response to HCC cells. Results demonstrate that “arming” oHSV may serve may serve as a novel treatment for patients with HCC.
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| Academic Significance and Societal Importance of the Research Achievements |
第三世代制限増殖型遺伝子組換えHSV-1を用いたウイルス療法は、投与後にウイルスが腫瘍内で増幅するという癌細胞に共通した細胞生物学的機構を利用するため、癌化の遺伝学的背景に関わらず、様々ながん種に適用できる。抗腫瘍免疫を増強する機能付加型のT-mfIL12,T-B7-1は、T-01より格段に増強した抗腫瘍効果を示した。抗腫瘍免疫における重要性が認識されてきたサイトカイン発現の遺伝子を用いた新たな増殖型治療ベクターの開発は、抗腫瘍効果の向上の面において意義が大きい。基礎的データを収集する事により、肝細胞癌をも根治可能にする、革新的かつ実用的な新規治療の開発研究を推進する。
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