Molecular understanding of tumor immunology of malignant pleural mesothelioma targeting human CD26/DPPIV molecule.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07683
• 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: Juntendo University
• Principal Investigator: Hatano Ryo 順天堂大学, 大学院医学研究科, 特任准教授 (30638789)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CD26/DPP4 / 悪性胸膜中皮腫 / ヒト化抗CD26抗体 / 腫瘍免疫 / ヒトT細胞 / 全身性エリテマトーデス

Outline of Final Research Achievements

CD26 is a human T cell costimulatory molecule with known dipeptidyl peptidase 4 (DPP4) activity and is expressed on both T cells and various types of tumor cells. We have had a long-standing interest in the role of CD26 in cancer biology and immune regulation and developed a humanized anti-CD26 monoclonal antibody (mAb). The phase I/II clinical trial of this mAb for malignant pleural mesothelioma (MPM) has been finished. In addition to the direct anti-tumor effects of anti-CD26 mAb on CD26-expressing tumors, this mAb is expected to positively regulate tumor immunity.
In the present study, we investigate the expression pattern of CD26 and the response to CD26-mediated costimulation of human T cells in the pleural effusion that are located near MPM to clarify how CD26 molecule is involved in the regulation of tumor immunity. The aim of the study is to elucidate the novel mechanisms of action of anti-CD26 mAb and to establish anti-CD26 mAb therapy for the refractory tumors including MPM.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

がん細胞自身や抑制性の免疫細胞の影響により、がん細胞周囲のT細胞と末梢血T細胞とでは性質が大きく異なり、がん組織の免疫細胞の機能解析が推奨されているが、新鮮な組織を得る難しさや細胞数の制限など研究上の制約も多いことが課題である。
がん細胞の近位に存在する胸水中T細胞を用いた本研究により、CD26分子が腫瘍免疫の制御にいかに関与しているかを明らかにし、CD26抗体の新たな抗腫瘍作用メカニズムの解明に貢献することで、悪性胸膜中皮腫を中心とした難治性がんに対する革新的なCD26抗体療法の確立を目指す。