Secretome analysis of tumor microenvironment for developing immunotherapeutics

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07184
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Juntendo University
• Principal Investigator: Fukuhara Takeshi 順天堂大学, 医学(系)研究科(研究院), 准教授 (20359673)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 抗体 / メラノーマ / 血管新生 / Secretome

Outline of Final Research Achievements

This study aimed to reveal the molecular mechanism underlying melanoma tumorigenesis. As melanoma biomarker, IL13Ra2 was identified by our functional antibody screening method. To reveal the function of gain or loss of IL13Ra2 expression, in vitro and in vivo experiments including Secretome analysis. Then, it has been discovered that over expression of AREG in the Xenografted tissue with IL13Ra2-positive melanoma cells. Histopathological analysis identified extended growth of CD31-positive endothelial cells in Xenograft mice, suggesting IL13Ra2-AREG axis enhance tumor angiogenesis (Okamoto et al., Sci. Report 2019). Our approach to generate antibody therapeutics was targeted on IL13Ra2 and AREG, so that several hybridoma producing anti-human or mouse AREG proteins were screened. Neutralization activity as well as immunoreactivity of antigenic peptides were on-going.

Free Research Field

抗体治療

Academic Significance and Societal Importance of the Research Achievements

本研究は難治疾患に該当する悪性黒色腫について、がんを標的とした抗癌剤治療に制限が生じている現状を鑑みて、がん微小環境を構成する他の種類である間質細胞に着目した新しい抗体治療の基礎的知見を得ようとするものである。IL13Ra2を悪性黒色腫の新しいバイオマーカーに同定していたが、この悪性化に至る分子メカニズムを同定して、当該分子AREGに対する治療抗体を探索しようと試みた。特にIL13Ra2とAREGの発現協調性について解析も行い、学会発表および論文として発表を行った。