Epithelial mesenchymal transition (EMT)-associated proteins as potent immunotherapeutic target for canner immunotherapy
| Project/Area Number |
19K07452
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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 49020:Human pathology-related
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | HLA / ペプチド / T-cell / ビメンチン / リン酸化 / EMT / 大腸癌 / エピトープ / ビメンチN / T cell / 腫瘍免疫 |
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| Outline of Research at the Start |
本研究では、難治再発転移癌に対する先進的な癌免疫療法を確立するために、癌の上皮間葉転換（epithelial-mesenchymal transition:EMT）関連分子を標的とした高い免疫原性を有する抗原ペプチドを探索し、癌治療における有用性を検討する。具体的には、EMT癌細胞で過剰発現されるEMT関連分子を標的とし、癌細胞を特異的に殺傷するT細胞を増殖させることが可能な抗原ペプチドを同定するとともに、難治再発転移癌患者においてEMT関連分子が免疫系の標的分子になりうるかを検討する。
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| Outline of Final Research Achievements |
During metastasis, cancer cells often obtain unique characteristics such as epithelial-mesenchymal transition (EMT). Vimentin is one of the biomarkers that contributes to EMT by changing cell shape and motility. Since abnormal phosphorylation is a hallmark of malignancy, targeting phosphorylated vimentin is a feasible approach for the treatment of metastatic tumors.Here, we showed that the expression of phosphorylated vimentin was upregulated in metastatic sites of Colorectal cancer (CRC). The novel phosphorylated helper peptide epitopes from vimentin could elicit sufficient T cell response. Notably, precursor lymphocytes which specifically reacted to these phosphorylated vimentin-derived peptides were detected in CRC patients.
These results suggested that immunotherapy targeting phosphorylated vimentin could be a novel therapeutic agent for metastatic CRC patients.
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| Academic Significance and Societal Importance of the Research Achievements |
再発転移癌の克服に向けたEMT関連分子特異的T細胞の活性化を基軸とした革新的次世代型癌ワクチン療法を確立するために、EMT関連分子であるビメンチンにおけるT細胞認識抗原ペプチドを探索しそれらの臨床学的有効性について明らかにするとともに大腸癌患者におけるリン酸化ビメンチンに対する免疫応答性について明らかにした。
癌が全身の諸臓器に多数再発転移している患者群では、既存の治療効果が乏しいことから、再発転移癌に対する有効かつ革新的な免疫療法の標的にEMT関連分子の一つであるビメンチンが、有望な癌抗原ペプチドワクチンの候補になりうると考えられた。
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Report
(4 results)
Research Products
(3 results)
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[Journal Article] Phosphorylated vimentin as an immunotherapeutic target against metastatic colorectal cancer.2019
Author(s)
Ohara M, Ohara K, Kumai T, Ohkuri T, Nagato T, Hirata-Nozaki Y, Kosaka A, Nagata M, Hayashi R, Harabuchi S, Yajima Y, Oikawa K, Harabuchi Y, Sumi Y, Furukawa H, Kobayashi H.
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Journal Title
Cancer Immunol Immunother.
Volume: ePub
Issue: 6
Pages: 989-999
DOI
Related Report
Peer Reviewed / Open Access
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