2023 Fiscal Year Final Research Report
Study on enhancement of efficacy of HPV-targeted cancer vaccine against precancer lesions of cervical cancer
| Project/Area Number |
21K09553
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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 56040:Obstetrics and gynecology-related
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| Research Institution | Nihon University |
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Principal Investigator |
KAWANA Kei 日本大学, 医学部, 教授 (60311627)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 子宮頸癌 / HPV / 癌ワクチン / 粘膜免疫 / 子宮頸部高度上皮内腫瘍 / 第I/II相医師主導治験 / E7発現乳酸菌製剤 / コンパニオン診断 |
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| Outline of Final Research Achievements |
A therapeutic HPV vaccine, IGMKK16E7, was developed as an immunotherapy (cancer vaccine) targeting HPV oncoprotein E7, which is highly expressed in the precancerous lesion CIN2/3, and is a lactic acid bacteria (Lactobacillus casei) preparation expressing HPV16 E7. Patients with high CD86 expression in cervical cells showed poor effector cell efficacy, while patients with low CD86 expression showed enhanced efficacy. CD86 and CTLA-4 expression were positively correlated and presumed to suppress T cells at the local environment. Patients with low CD86 expression were expected to have high efficacy of IGMKK16E7. CD86-low is a pre-treatment predictive biomarker of histological complete regression by IGMKK16E7.
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| Free Research Field |
産婦人科、婦人科腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
我々は、世界初の治療的HPVワクチンの開発を行っている。第I/II相ランダム化比較試験の結果から、プラセボ群と比べてIGMKK16E7（高用量群）において、有意なCIN2/3の治癒効果を示した。本研究によって、治療前のCIN2/3患者の子宮頸部でCD86低発現の症例を選択することがIGMKK16E7による治療をより効果的にすることを示した。抗CTLA-4抗体でCD86/CTLA-4経路を阻害することで、IGMKK16E7の効果を増強することが期待される。CIN2/3に対する子宮頸部円錐切除術後の早産リスクがIGMKK16E7内服によって回避できる点は社会的意義が大きい。
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