| Project/Area Number |
17K16865
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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 |
Obstetrics and gynecology
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| Research Institution | Nihon University (2018)
Saitama Medical University (2017) |
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Principal Investigator |
IKEDA Yuji 日本大学, 医学部, 助教 (80713453)
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | がん精巣抗原 / 免疫療法 / 婦人科癌 / ペプチドワクチン / アンチゲン |
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| Outline of Final Research Achievements |
Firstly, mRNA sequencing data obtained from 582 samples of endometrial cancer and 53 control samples from 31 normal organs were extracted from cancer genome atlas (TCGA) database and Genotype-Tissue Expression project, respectively. After filtering of protein coding genes, 8 to 12 peptides with high binding affinity to HLA-A*24 and -A*02 alleles were identified. Analysis of binding affinity revealed that 21 and 146 peptides derived-from ten genes of interest showed high binding affinity to those HLA. Remarkably, RGPD6 is the most reliable candidate target. Secondly, we conducted a phase I dose-escalation trial using a mixture of 5 peptides to vaccinate cervical cancer patients with HLA-A*2402. Interferon-γ enzyme-linked immunospot assays for each of the 5 antigens showed that 8 (89%) and 7 (78%) patients had high T-cell responses to FOXM1 and MELK, respectively. As a result, RGPG6, FOXM1 and MELK are seemed to be a strong candidate of immunotherapeutic target for gynecologic cancers.
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| Academic Significance and Societal Importance of the Research Achievements |
今回同定されたがんの特異性をターゲットとした免疫療法の開発は直接的にがん細胞を攻撃するアクセルの役割を担う事が大いに期待される。即ちこれらのターゲットを認識するT細胞を患者に投与する事で、がんを特異的に攻撃する免疫システムの構築が出来る可能性がある。加えて将来的には現在旺盛なチェックポイント阻害薬（免疫機構のブレーキを解除する意義がある）を併用する事でよりその効果も高める可能性があり、今後の研究開発の進展が期待される。
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