Anti KL-6 antibody enhances the effects of molecular targeted drug

• Project/Area Number: 23659433
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Hiroshima University
• Principal Investigator: KOHNO Nobuoki 広島大学, 医歯薬保健学研究院(医), 教授 (80215194)
• Co-Investigator(Renkei-kenkyūsha): HATTORI Noboru 広島大学, 医歯薬保健学研究院(医), 准教授 (00283169) ; ISHIKAWA Nobuhisa 広島大学, 医歯薬保健学研究院(医), 講師 (90423368)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: KL-6 / 分子標的治療薬 / 肺癌

Research Abstract

The aim of the present study was to investigate the additive effect of anti-KL-6 antibody on the therapeutic antibody-induced ADCC (Antibody-Dependent Cellular-Cytotoxicity) activity. The expression of HER2 and KL-6 were measured using FACS analysis in 4 cancer cell lines (SK-BR-3, ZR75-1, PC3, YMB-S), and both HER2 and KL-6 were highly expressed in YMB-S cells. Accordingly, the effects of anti KL-6 antibody on the ADCC activity of PBMCs evoked by Trastuzumab were examined using Cr-51 release assay. Enhanced cytotoxicity was observed in an effector-to-target ratio manner when YMB-S cells were treated with anti-KL-6 antibody. These findings indicate that anti KL-6 antibody can enhance the therapeutic antibody-induced ADCC activity mediated by mononuclear cells.

Research Products

• [Journal Article] Differences in serum SP-D levels between German and Japanese subjects are associated with SFTPD gene polymorphisms. (2014)
  • Author(s): Horimasu Y, Hattori N, Ishikawa N, Tanaka S, Bonella F, Ohshimo S, Guzman J, Costabel U, Kohno N
  • Journal Title: BMC Med Genet Volume: 15 Issue: 1 Pages: 4-4
  • DOI: 10.1186/1471-2350-15-4
  • NAID: 120006799353
  • Peer Reviewed / Open Access
• [Journal Article] SK-216, an inhibitor of plasminogen activator inhibitor-1, limits tumor progression and angiogenesis (2013)
  • Author(s): Masuda T, Hattori N, Senoo T, Akita S, Ishikawa N, Fujitaka K, Haruta Y, Murai H, Kohno N
  • Journal Title: Mol Cancer Ther Volume: 12 Pages: 2378-88
  • Peer Reviewed
• [Journal Article] SK-216, an inhibitor of plasminogen activator inhibitor-1, limits tumor progression and angiogenesis. (2013)
  • Author(s): Masuda T, Hattori N, Senoo T, Akita S, Ishikawa N, Fujitaka K, Haruta Y, Murai H, Kohno N.
  • Journal Title: Mol Cancer Ther Volume: 12 Issue: 11 Pages: 2378-88
  • DOI: 10.1158/1535-7163.mct-13-0041
  • Peer Reviewed
• [Journal Article] Characteristics of inspiratory and expiratory reactance in interstitial lung disease. (2013)
  • Author(s): Sugiyama A, Hattori N, Haruta Y, Nakamura I, Nakagawa M, Miyamoto S, Onari Y, Iwamoto H, Ishikawa N, Fujitaka K, Murai H, Kohno N.
  • Journal Title: Respir Med Volume: 107 Issue: 6 Pages: 875-82
  • DOI: 10.1016/j.rmed.2013.03.005
  • Peer Reviewed
• [Journal Article] A nationwide epidemiological survey of chronic hypersensitivity pneumonitis in Japan. (2013)
  • Author(s): Okamoto T, Miyazaki Y, Ogura T, Chida K, Kohno N, Kohno S, Taniguchi H, Akagawa S, Mochizuki Y, Yamauchi K, Takahashi H, Johkoh T, Homma S, Kishi K, Ikushima S, Konno S, Mishima M, Ohta K, Nishioka Y, Yoshimura N, Munakata M, Watanabe K, Miyashita Y, Inase N.
  • Journal Title: Respir Investig Volume: 51 Pages: 191-199
  • Peer Reviewed
• [Journal Article] RASEF is a novel diagnostic biomarker and a therapeutic target for lung cancer. (2013)
  • Author(s): Oshita H, Nishino R, Takano A, Fujitomo T, Aragaki M, Kato T, Akiyama H, Tsuchiya E, Kohno N, Nakamura Y, Daigo Y.
  • Journal Title: Mol Cancer Res Volume: 11 Issue: 8 Pages: 937-951
  • DOI: 10.1158/1541-7786.mcr-12-0685-t
  • Peer Reviewed
• [Journal Article] Cross-sectional and prospective study of the association between lung function and prediabetes (2013)
  • Author(s): Yamane T, Yokoyama A, Kitahara Y*, Miyamoto S, Haruta Y, Hattori N, Yamane K, Hara H, Kohno N
  • Journal Title: BMJ Open Volume: 3 Issue: 2 Pages: 3-3
  • DOI: 10.1136/bmjopen-2012-002179
  • NAID: 120006799354
  • Peer Reviewed
• [Journal Article] Krebs von den Lungen-6 (KL-6) is a prognostic biomarker in patients with surgically resected non-small cell lung cancer. (2012)
  • Author(s): Tanaka S, et al.
  • Journal Title: International journal of cancer Volume: 130 Issue: 2 Pages: 377-387
  • DOI: 10.1002/ijc.26007
  • Peer Reviewed
• [Journal Article] Interferon (alpha, beta and omega) receptor 2 is a prognostic biomarker for lung cancer (2012)
  • Author(s): Tanaka S, Hattori N, Ishikawa N, Horimasu Y, Deguchi N, Takano A, Tomoda Y, Yoshioka K, Fujitaka K, Arihiro K, Okada M, Yokoyama A, Kohno N
  • Journal Title: Pathobiology Volume: 79 Issue: 1 Pages: 24-33
  • DOI: 10.1159/000331230
  • Peer Reviewed
• [Journal Article] Different MUC1 gene polymorphisms in German and Japanese ethnicities affect serum KL-6 levels (2012)
  • Author(s): Horimasu Y, Hattori N, Ishikawa N, K awase S, Tanaka S, Yoshioka K, Yokoy ama A, Kohno N, Bonella F, Guzman J, Ohshimo S, Costabel U
  • Journal Title: Respir Med Volume: 106 Issue: 12 Pages: 1756-64
  • DOI: 10.1016/j.rmed.2012.09.001
  • Peer Reviewed
• [Journal Article] Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases (2012)
  • Author(s): Ishikawa N, Hattori N, Yokoyama A, Kohno N
  • Journal Title: Respir Investig Volume: 50 Issue: 1 Pages: 3-13
  • DOI: 10.1016/j.resinv.2012.02.001
  • Peer Reviewed
• [Journal Article] Comparison of serum KL-6 versus bronchoalveolar lavage neutrophilia for the diagnosis of bronchiolitis obliterans in lung transplantation. (2011)
  • Author(s): Ohshimo S, Bonella F, Sommerwerck U, Teschler H, Kamler M, Jakob HG, Kohno N, Guzman J, Costabel U.
  • Journal Title: J Heart Lung Transplant Volume: 30 Issue: 12 Pages: 1374-1380
  • DOI: 10.1016/j.healun.2011.07.010
  • Peer Reviewed
• [Journal Article] Change in serum KL-6 level from baseline is useful for predicting life-threatening EGFR-TKIs induced interstitial lung disease (2011)
  • Author(s): Kawase S, et al
  • Journal Title: Respir Res Volume: 12 Issue: 1 Pages: 97-97
  • DOI: 10.1186/1465-9921-12-97
  • Peer Reviewed
• [Journal Article] Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma. (2011)
  • Author(s): Ishikawa N, Mazur W, Toljamo T, Vuopala K, Rönty M, Horimasu Y, Kohno N, Kinnula VL.
  • Journal Title: BMC Pulm Med Volume: 11 Issue: 1 Pages: 22-22
  • DOI: 10.1186/1471-2466-11-22
  • Peer Reviewed
• [Journal Article] Levels of Surfactant proteins A and D, and KL-6 are elevated in the induced sputum of COPD ; a sequential sputum analysis (2011)
  • Author(s): Ishikawa N, et al
  • Journal Title: Respiration Volume: 82 Issue: 1 Pages: 10-18
  • DOI: 10.1159/000324539
  • Peer Reviewed
• [Journal Article] KL-6 concentration in pulmonary epithelial lining fluid is a useful prognostic indicator in patients with acute respiratory distress syndrome. (2011)
  • Author(s): Kondo T, Hattori N, Ishikawa N, Murai H, Haruta Y, Hirohashi N, Tanigawa K, Kohno N.
  • Journal Title: Respir Res Volume: 12 Issue: 1 Pages: 32-32
  • DOI: 10.1186/1465-9921-12-32
  • NAID: 120003692470
  • Peer Reviewed
• [Journal Article] Mucins carrying selectin ligands as predictive biomarkers of disseminated intravascular coagulation complication in ARDS (2011)
  • Author(s): Nakashima T, et al
  • Journal Title: Chest Volume: 139 Issue: 2 Pages: 296-304
  • DOI: 10.1378/chest.09-3082
  • Peer Reviewed
• [Presentation] Antitumor effect of a humanized antibody against aminopeptidase N in mouse tumor models (2013)
  • Author(s): Akita S, Hattori N, Ishikawa N, Fujitaka K, Haruta Y, Murai H, Kohno N
  • Organizer: 18th congress of the Asian Pacific Society of Respirology
  • Place of Presentation: 横浜
  • Year and Date: 2013-11-11
• [Presentation] Discovery and clinical application of KL-6, a circulating biomarker for interstitial lung diseases (2013)
  • Author(s): Kohno N
  • Organizer: 2013 European Respiratory Society Annual Congress
  • Place of Presentation: Barcelona Spain
  • Year and Date: 2013-09-07
• [Presentation] Discovery and clinical application of KL-6, a circulating biomarker for interstitial lung diseases. (2013)
  • Author(s): Kohno N.
  • Organizer: 2013 European Respiratory Society Annual Congress
  • Place of Presentation: バルセロナ、スペイン
  • Invited
• [Presentation] Gene expression profiles of chronic hypersensitivity pneumonitis: Molecular signatures of pulmonary fibrosis. (2013)
  • Author(s): Ishikawa N, Taniwaki M, Horimasu Y, Iwamoto H, Ohshimo S, Fujitaka K, Haruta Y, Murai H, Hattori N, Kohno N.
  • Organizer: American Thoracic society international Conference 2013
  • Place of Presentation: フィラデルフィア、アメリカ
• [Presentation] Ethnic difference in the incidence of acute exacerbation in idiopathic pulmonary fibrosis (2013)
  • Author(s): Ohshimo S, Ishikawa N, Horimasu Y, Fujitaka K, Haruta Y, Murai H, Hattori N, Bonella F, Kohno N, Guzman J, Costabel U.
  • Organizer: American Thoracic society international Conference 2013
  • Place of Presentation: フィラデルフィア、アメリカ
• [Presentation] Difference of serum SP-D levels between German and Japanese are associated with SFTP gene polymorphisms. (2013)
  • Author(s): Horimasu Y, Hattori N, Ishikawa N, Tanaka S, Bonella F, Ohshimo S, Guzman J, Costabel U, KohnoN.
  • Organizer: American Thoracic society international Conference 2013
  • Place of Presentation: フィラデルフィア、アメリカ
• [Presentation] KL-6, SP-D and MMP-7 as serum biomarkers for early detection of interstitial lung diseases. (2013)
  • Author(s): Ishikawa N, Yoshioka K, Horimasu Y, Iwamoto H, Ohshimo S, Hattori N, Kohno N.
  • Organizer: 2013 European Respiratory Society Annual Congress
  • Place of Presentation: バルセロナ、スペイン
• [Presentation] MUC1 gene polymorphisms are associated with serum KL-6 levels and pulmonary dysfunction in pulmonary alveolar proteinosis. (2013)
  • Author(s): Ohshimo S, Horimasu Y, Bonella F, Ishikawa N, Fujitaka K, Haruta Y, Murai H, Hirohashi N, Hattori N, Tanigawa K, KohnoN, Guzman J, Costabel U.
  • Organizer: 2013 European Respiratory Society Annual Congress
  • Place of Presentation: バルセロナ、スペイン
• [Presentation] KL-6 and CCL18 as predictors for acute exacerbation in idiopathic pulmonary fibrosis. (2012)
  • Author(s): Ohshimo S , Horimasu Y, Bonella F, Ishikawa N, Hattori N, Tanigawa K, Kohno N, Guzman J, Costabel U.
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: San Francisco（アメリカ.)
• [Presentation] Different serum cut-off values of KL-6 for German and Japanese to diagnose iIdiopathic interstitial pneumonias are related to different Mucin-1 gene polymorphisms. (2012)
  • Author(s): Horimasu Y, Hattori N, Ishikawa N, Tanaka S, Yoshioka K, Bonella F, Ohshimo S, Guzman J, Kohno N, Costabel U.
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: San Francisco（アメリカ.)
• [Presentation] Different cutoff values of serum SP-D for German and Japanese to diagnose idiopathic interstitial pneumonias are related to different SFTPD gene polymorphisms. (2012)
  • Author(s): Horimasu Y, Hattori N, Ishikawa N, Tanaka S, Yoshioka K, Bonella F, Ohshimo S, Guzman J, Costabel U, Kohno N.
  • Organizer: European Respiratory Society Annual Congress
  • Place of Presentation: Vienna（オーストリア）
• [Presentation] KL-6 is a useful serum biomarker for early detection of interstitial lung disease. (2012)
  • Author(s): Kohno N, Ishikawa N, Deguchi N, Iwamoto H, Ohshimo S, Fujitaka K, Haruta Y, Murai H, Hattori N.
  • Organizer: European Respiratory Society Annual Congress
  • Place of Presentation: Vienna（オーストリア)
• [Presentation] Gene expression profiles of idiopathic interstitial pneumonias: Identification of disease-specific diagnostic markers and molecular therapeutic targets. (2012)
  • Author(s): Ishikawa N, Hattori N, Taniwaki M, Horimasu Y, Matsuda T, Kohno N.
  • Organizer: European Respiratory Society Annual Congress
  • Place of Presentation: Vienna（オーストリア）
• [Presentation] Krebs von den Lungen-6 (KL-6) is a prognostic biomarker in patients with surgically resected nonsmall cell lung cancer (2011)
  • Author(s): Tanaka S, Ishikawa N, Hattori N, Hamada H, Yokoyama A, Kohno N
  • Organizer: 2011 European Respiratory Society Annual Congress
  • Place of Presentation: Amsterdam, Netherlands
  • Year and Date: 2011-09-24
• [Presentation] Serum KL-6 is a useful diagnostic and prognostic biomarker in idiopathic interstitial pneumonia in German patients. (2011)
  • Author(s): Horimasu Y, Ohshimo S, Ishikawa N, Tanaka S, Yoshioka K, Bonella F, Hattori N, Kohno N, Guzman J, Costabel U.
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: Denver, U.S.A.
• [Presentation] Krebs von den lungen-6 (KL-6) is a useful biomarker for life threatening EGFR-TKI related interstitial lung disease (2011)
  • Author(s): Kawase S, Hattori N, Ishikawa N, Horimasu Y, Furonaka O, Isobe T, Hamada H, Yokoyama A, Kohno N
  • Organizer: American Thoracic Society International Conference
  • Place of Presentation: Denver, U.S.A.
• [Presentation] nterferon (-alpha, -beta, and -omega) receptor 2 (IFNAR2) is a prognostic biomarker for lung cancer. (2011)
  • Author(s): Ishikawa N, Hattori N, Tanaka S, Horimasu Y, Yokoyama A, Kohno N.
  • Organizer: European Respiratory Society Annual Congress
  • Place of Presentation: Amsterdam, Netherlands
• [Presentation] Serum SP-A and SP-D: different cutoff values for German and Japanese patients to diagnose idiopathic interstitial pneumonia. (2011)
  • Author(s): Horimasu Y, Hattori N, Ishikawa N, Tanaka S, Yoshioka K, Ohshimo S, Bonella F, Guzman J, Costabel U, Kohno N.
  • Organizer: European Respiratory Society Annual Congress
  • Place of Presentation: Amsterdam, Netherlands
• [Presentation] Reliability of ATS/ERS criteria for the diagnosis of idiopathic pulmonary fibrosis. (2011)
  • Author(s): Ohshimo S, Bonella F, Tanigawa K, Kohno N, Guzman J, Costabel U.
  • Organizer: European Respiratory Society Annual Congress
  • Place of Presentation: Amsterdam, Netherlands
• [Book] がんの浸潤・転移 (2011)
  • Author(s): 石川暢久，河野修興
  • Total Pages: 241
  • Publisher: 南山堂