2023 Fiscal Year Final Research Report
Therapeutic efficacy of triple-mutated oncolytic HSV-1 armed with IL-12 for bone invasion in oral squamous cell carcinoma
| Project/Area Number |
21K10137
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
犬伏 俊博 大阪大学, 歯学部附属病院, 講師 (30550941)
伊藤 博崇 東京大学, 医科学研究所, 助教 (30863815)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | がんウイルス療法 |
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| Outline of Final Research Achievements |
OSCC is frequently associated with bone invasion, which lowers the quality of life and worsens prognosis. IL-12, a well-known immunostimulatory cytokine, has been shown to suppress osteoclast differentiation in vitro. In this study, we evaluated the suppression effect of an oncolytic HSV-1 armed with murine IL-12 (T-mfIL12) on tumor growth and bone resorption in C3H/He mice with orthotopic OSCC. This model shows gradual mandibular bone invasion mimicking the clinical settings. T-mfIL12 or T-01 (5.0 × 105 pfu) was administered into the formed mass adjacent to the mandibular periosteum 7 days after SCCVII implantation. T-mfIL12-treated mice had significantly longer survival than those treated with T-01. Micro-computed tomography showed that T-mfIL12, unlike T-01, significantly suppressed the bone resorption compared with mock. The results suggest that IL-12 expressing oncolytic HSV-1 may be useful for suppressing bone invasion as well as inhibiting tumor progression in OSCC patients.
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| Free Research Field |
口腔癌のウイルス療法
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| Academic Significance and Societal Importance of the Research Achievements |
口腔癌の顎骨浸潤に対しては、顎骨切除を主とした外科的治療が標準治療であるが、超高齢化社会の現在、適応できない患者も多く、また外科的切除後のQOLの低下は著しく非侵襲的治療が切望されている。IL-12発現型がん治療用HSV-1（T-mfIL-12）は本邦で悪性黒色腫に対する臨床試験が行われており、目覚ましい効果を得ている。悪性黒色腫と同じく、視診触診可能な口腔癌に対して、T-mfIl-12は投与しやすいと考えられ、本研究成果より、IL-12の持つ抗腫瘍免疫賦活化効果に加え、骨吸収抑制効果が加わることにより、T-mfIL-12は強力な非侵襲的治療法に近い将来なり得ると考えられる。
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