Development of therapeutic antibodies based on the elevated S100A8/A9 in tumor microenvironment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07636
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Okayama University
• Principal Investigator: Kinoshita Rie 岡山大学, 医歯薬学域, 助教 (40518297)
• Co-Investigator(Kenkyū-buntansha): 阪口 政清 岡山大学, 医歯薬学域, 教授 (70379840) ; 小林 和子 岡山大学, 医歯薬学域, 助教 (20304298)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: antibody / inflammation / cancer / metastasis

Outline of Final Research Achievements

S100A8/A9 (S100A8 and A9 heterodimer) is an inflammatory factor engaged in the onset of chronic inflammatory diseases. We analyzed patient plasma of several kinds of cancer and discovered excessive expression of S100A8/A9. Using RNA-seq analysis, we confirmed that stimulation of S100A8/A9 on macrophages induced upregulation of many types of cancer-associated cytokines and chemokines. Therefore, we have developed prominent new anti-human S100A8/A9 monoclonal antibody for treatment of cancer. We confirmed the therapeutic effect of our developed S100A8/A9 neutralizing antibody in subcutaneous pancreatic tumor mouse model. The antibody can terminate the negative spiral of aggravated inflammation induced by S100A8/A9, which in turn alleviates cancer progression.

Free Research Field

タンパク質工学

Academic Significance and Societal Importance of the Research Achievements

開発した抗S100A8/A9抗体は、強力な抗炎症作用をもち、様々な炎症性疾患治療薬として実用化される可能性をもつ。先行してIPF(特発性肺線維症)およびIPF急性増悪について有意な治療効果を示し、ヒト化抗体を作製している。本研究成果により、RNA-seq解析の手法を用いて、S100A8/A9が炎症性疾患を増悪するメカニズムの一端が解明され、マウスモデルの実験データからがん転移治療薬としての開発抗体の可能性が示された。