Epithelial mesenchymal transition (EMT)-associated proteins as potent immunotherapeutic target for canner immunotherapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07452
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: Kobayashi Hiroya 旭川医科大学, 医学部, 教授 (90280867)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: HLA / ペプチド / T-cell / ビメンチン / リン酸化 / EMT / 大腸癌

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.

Free Research Field

免疫学

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。