Development of innovative therapeutic antibodies targeting the inflammatory tumor microenvironment in refractory thoracic tumors

• Project/Area Number: 18K19581
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Okayama University
• Principal Investigator: Toyooka Shinichi 岡山大学, 医歯薬学総合研究科, 教授 (30397880)
• Co-Investigator(Kenkyū-buntansha): 枝園 和彦 岡山大学, 大学病院, 助教 (30708079) ; 宗 淳一 近畿大学, 医学部, 准教授 (90559890) ; 山本 寛斉 岡山大学, 大学病院, 助教 (40467733) ; 冨田 秀太 岡山大学, 大学病院, 准教授 (10372111) ; 諏澤 憲 岡山大学, 大学病院, 助教 (90839713)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 肺癌 / 癌微小環境 / 炎症 / 抗体療法 / 胸部悪性腫瘍

Outline of Final Research Achievements

The purpose of this study was to elucidate the pathophysiology related to inflammatory mediator proteins in the cancer tumor microenvironment, including cancer cells, stromal cells and immune cells, and to develop new therapeutic strategies. We showed that active fibroblasts induce activation of the STAT3 pathway in lung cancer cells, promoting cancer progression and the acquisition of drug resistance. The inflammatory mediators, S100A8 / 9 protein and HMGB1 protein, activate the proliferation and function of fibroblasts, promote the growth of cancer cells. These activations are suppressed by the administration of their respective neutralizing antibodies.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、難治性疾患の一つである肺癌をはじめとする癌微小環境における慢性炎症を一因とする胸部悪性腫瘍に対する、既存の化学療法や分子標的薬とはまったく機序の異なる新規治療法の開発につながる成果と考えられる。特に肺癌は日本において最も死亡者数の多い癌であり、肺癌の治療成績の向上は社会的にも意義が大きいと考えられる。

Research Products

• [Presentation] Clinicopathological characteristics of lung cancer patients with concomitant idiopathic pulmonary fibrosis (2019)
  • Author(s): Kota Araki, Kazuhiko Shien, Shunsaku Miyauchi, Akihiro Miura, Yuta Takahashi, Eisuke Kurihara, Yusuke Ogoshi, Kei Namba, Ken Suzawa, Hiromasa Yamamoto, Shuta Tomida, Junichi Soh, Masakiyo Sakaguchi, Shinichi Toyooka
  • Organizer: AACR Annual Meeting 2019
  • Int'l Joint Research