Large molecular complex of cell surface in malignant pleural mesotheliom as a novel treatment target

• Project/Area Number: 15K15324
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Juntendo University
• Principal Investigator: OHNUMA Kei 順天堂大学, 医学(系)研究科(研究院), 准教授 (10396872)
• Co-Investigator(Kenkyū-buntansha): 岩田 哲史 順天堂大学, 医学(系)研究科(研究院), 非常勤講師 (00396871) ; 岩尾 憲明 順天堂大学, 医学部, 准教授 (00309139)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 悪性中皮腫 / CD26 / ソマトスタチン受容体 / ペリオスチン / CD26抗体療法 / dipeptydil peptidase 4 / ソマトスタチン

Outline of Final Research Achievements

Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm deriving from the pleural mesothelial lining. Despite the modest clinical benefit of a multimodality treatment approach including surgery, combination chemotherapy and radiation, prognosis remains grim with poor overall survival. New approaches based on deregulated pathways and targeted therapies are required to improve survival of MPM patients. We have had a long-standing interest in the role of CD26 in cancer biology and its suitability as a novel therapeutic target in selected neoplasms. Our previous work demonstrated that CD26 is preferentially expressed in MPM cells but not in normal mesothelial cells. Recently, we reported robust in vivo data on the anti-tumor activity of anti-CD26 monoclonal antibody in mouse xenograft models. We herein showed significant novel findings and the early clinical development of a CD26-targeted therapy for MPM, advances that can lead to a more hopeful future for MPM patients.

Research Products

• [Int'l Joint Research] フロリダ大学/ヴァンダービルト大学(米国)
• [Int'l Joint Research] フロリダ大学(米国)
• [Journal Article] First-in-human phase 1 of YS110, a monoclonal antibody directed against CD26 in advanced CD26-expressing cancers (2017)
  • Author(s): Angevin, E. Isambert, N. Trillet-Lenoir, V. You, B. Alexandre, J. Zalcman, G. Vielh, P. Farace, F. Valleix, F. Podoll, T. Kuramochi, Y. Miyashita, I. Hosono, O. Dang, N. H. Ohnuma, K. Yamada, T. Kaneko, Y. Morimoto, C.
  • Journal Title: Br J Cancer Volume: 印刷中 Issue: 9 Pages: 1-9
  • DOI: 10.1038/bjc.2017.62
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A possible role for CD26/DPPIV enzyme activity in the regulation of psoriatic pruritus (2017)
  • Author(s): Komiya, E. Hatano, R. Otsuka, H. Itoh, T. Yamazaki, H. Yamada, T. Dang, N. H. Tominaga, M. Suga, Y. Kimura, U. Takamori, K. Morimoto, C. Ohnuma, K.
  • Journal Title: J Dermatol Sci Volume: 印刷中 Issue: 3 Pages: 212-221
  • DOI: 10.1016/j.jdermsci.2017.03.005
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Development of New Therapy for Malignant Mesothelioma Based on CD26 Molecule (2016)
  • Author(s): Morimoto, C. Ohnuma, K.
  • Journal Title: Gan To Kagaku Ryoho Volume: 43 Pages: 855-62
• [Journal Article] Inhibition of VEGF-dependent angiogenesis by the anti-CD82 monoclonal antibody 4F9 through regulation of lipid raft microdomains (2016)
  • Author(s): Nomura, S. Iwata, S. Hatano, R. Komiya, E. Dang, N. H. Iwao, N. Ohnuma, K. Morimoto, C.
  • Journal Title: Biochem Biophys Res Commun Volume: 474 Issue: 1 Pages: 111-7
  • DOI: 10.1016/j.bbrc.2016.04.081
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of IL-26+CD26+CD4 T Cells in Pulmonary Chronic Graft-Versus-Host Disease and Treatment with Caveolin-1-Ig Fc Conjugate (2016)
  • Author(s): Ohnuma, K. Hatano, R. Itoh, T. Iwao, N. Dang, N. H. Morimoto, C.
  • Journal Title: Crit Rev Immunol Volume: 36 Issue: 3 Pages: 239-267
  • DOI: 10.1615/critrevimmunol.2016018772
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Remission of remitting seronegative symmetrical synovitis with pitting edema after unrelated cord blood transplantation for myelodysplastic syndrome. (2015)
  • Author(s): Ishii H, Konuma T, Ohnuma K, Hosono O, Tanaka H, Kato S, Tojo A, Takahashi S.
  • Journal Title: Ann Hematol. Volume: 95 Issue: 3 Pages: 523-524
  • DOI: 10.1007/s00277-015-2555-0
  • Peer Reviewed
• [Journal Article] CD26-mediated induction of EGR2 and IL-10 as potential regulatory mechanism for CD26 costimulatory pathway. (2015)
  • Author(s): Hatano R, Ohnuma K, Otsuka H, Komiya E, Taki I, Iwata S, Dang NH, Okumura K, Morimoto C.
  • Journal Title: J Immunol. Volume: Vol 194 Issue: 3 Pages: 960-72
  • DOI: 10.4049/jimmunol.1402143
  • Peer Reviewed / Open Access
• [Journal Article] Deep venous thrombosis was not detected after total knee arthroplasty in Japanese patients with haemophilia. (2015)
  • Author(s): Takedani H, Ohnuma K, Hirose J.
  • Journal Title: Haemophilia Volume: 21 Issue: 5 Pages: 585-588
  • DOI: 10.1111/hae.12643
  • Peer Reviewed
• [Journal Article] Regulation of Pulmonary Graft-versus-Host Disease by IL-26+CD26+CD4 T Lymphocytes. (2015)
  • Author(s): Ohnuma K, Hatano R, Aune TM, Otsuka H, Iwata S, Dang NH, Yamada T, Morimoto C.
  • Journal Title: J Immunol Volume: 194(8) Issue: 8 Pages: 3697-712
  • DOI: 10.4049/jimmunol.1402785
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Modulation of immunological responses and amelioration of collagen-induced arthritis by the novel roxithromycin derivative 5-I. (2015)
  • Author(s): Otsuki N, Iwata S, Yamada T, Hosono O, Dang NH, Hatano R, Ohnuma K, Morimoto C.
  • Journal Title: Modern Rheumatology Volume: 25 Pages: 562-570
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Role of Cas-L/NEDD9 as a Regulator of Collagen-induced Arthritis in a Murine Model (2015)
  • Author(s): Tomoki Katayose, Satoshi Iwata, Naoki Oyaizu, Osamu Hosono, Taketo Yamada, Nam H Dang, Ryo Hatano, Hirotoshi Tanaka, Kei Ohnuma, Chikao Morimoto
  • Journal Title: Biochem Bilphys Res Commun Volume: 印刷中 Issue: 4 Pages: 1069-75
  • DOI: 10.1016/j.bbrc.2015.03.156
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Book] Horizons in Cancer Research (2017)
  • Author(s): Ohnuma, K. Hatano, R. Yamazaki, H. Kaneko, Y. Dang, N. H. Morimoto, C.
  • Total Pages: 212
  • Publisher: Nova Science Publishers, Inc.