Development of a novel antibody therapy based on antibody-dependent cellular cytotoxicity activity against lung cancer and mesothelioma and identification of the immunological biomarkers
Project/Area Number |
24390210
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | The University of Tokushima |
Principal Investigator |
NISHIOKA Yasuhiko 徳島大学, ヘルスバイオサイエンス研究部, 教授 (70274199)
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Co-Investigator(Kenkyū-buntansha) |
KATO Yukinari 東北大学, 医学(系)研究科(研究院), 教授 (00571811)
KAKIUCHI Soji 徳島大学, 病院, 講師 (50380100)
GOTO Hisatsugu 徳島大学, 大学院ヘルスバイオサイエンス研究部, 講師 (00437641)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Project Status |
Completed (Fiscal Year 2014)
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Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2012: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | 抗体療法 / ADCC / ポドプラニン / 肺癌 / 悪性胸膜中皮腫 / 免疫療法 / バイオマーカー / 抗体治療 |
Outline of Final Research Achievements |
We developed novel antibodies against podoplanin expressing in lung squamous cell carcinoma and mesothelioma. We generated a human-rat chimeric anti-podoplanin antibody NZ-8 which showed higher anti-tumor activity in mouse xenograft model based on antibody-dependent cellular and complement- dependent cytotoxicity as compared to those of the rat antibody NZ-1. The binding activity of NZ-8 seemed to be higher against podoplanin expressing in tumor cells rather than normal cells such as alveolar cells or podocytes, indicating the advantage for clinical use of NZ-8. We finally developed the chimeric antibody NZ-12 showing the higher anti-tumor activity than NZ-8. Furthermore, gene expression analyses in xenograft tumors treated with NZ-1 identified the candidate genes related with the biological activity of NZ-1/NZ-8.
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Report
(4 results)
Research Products
(69 results)
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[Journal Article] Surfactant protein A suppresses lung cancer progression by regulating the polarization of tumor-associated macrophages.2013
Author(s)
Mitsuhashi A, Goto H, Kuramoto T, Tabata S, Yukishige S, Abe S, Hanibuchi M, Kakiuchi S, Saijo A, Aono Y, Uehara H, Yano S, Ledford JG, Sone S, Nishioka Y
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Journal Title
Am J Pathol
Volume: 182
Pages: 1843-1853
DOI
Related Report
Peer Reviewed
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[Journal Article] A novel targeting therapy of malignant mesothelioma using anti-podoplanin antibody.2013
Author(s)
Abe S, Morita Y, Kaneko MK, Hanibuchi M, Tsujimoto Y, Goto H, Kakiuchi S, Aono Y, Huang J, Sato S, Kishuku M, Taniguchi Y, Azuma M, Kawazoe K, Sekido Y, Yano S, Akiyama SI, Sone S, Minakuchi K, Kato Y, Nishioka Y
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Journal Title
J Immunol
Volume: 190
Pages: 6239-6249
DOI
Related Report
Peer Reviewed
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[Journal Article] Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR-activating and gatekeeper mutations.2013
Author(s)
Yamada T, Takeuchi S, Fujita N, Nakamura A, Wang W, Li Q, Oda M, Mitsudomi T, Yatabe Y, Sekido Y, Yoshida J, Higashiyama M, Noguchi M, Uehara H, Nishioka Y, Sone S, Yano S
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Journal Title
Oncogene
Volume: 32
Pages: 4427-4435
DOI
Related Report
Peer Reviewed
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[Presentation] ヒト小細胞肺癌骨転移に対するRANKL標的治療におけるIGF-1の関与2014
Author(s)
山子泰斗, 後東久嗣, 三橋惇志, 倉本卓哉, 田畑祥, 西條敦郎, 柿内聡司, 埴淵昌毅, 小川博久, 上原久典, 西岡安彦
Organizer
第23回日本がん転移学会学術集会
Place of Presentation
金沢市文化ホール(石川県金沢市)
Year and Date
2014-07-10
Related Report
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[Presentation] The role of fibrocytes in the resistance to anti-angiogenic therapy in malignant pleural mesothelioma and lung cancer2014
Author(s)
Hisatsugu Goto, Atsushi Mitsuhashi, Atsuro Saijo, Trung The Van, Yoshinori Aono, Hirohisa Ogawa, Soji Kakiuchi, Masaki Hanibuchi, Seiji Yano, Keisuke Izumi, Yasuhiko Nishioka
Organizer
ATS 2014 International Conference
Place of Presentation
San Diego Convention Center (U.S.A.)
Year and Date
2014-05-21
Related Report
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[Presentation] Surfactant protein A suppresses lung cancer progression by regulating tumor-associated macrophage polarization.
Author(s)
Hisatsugu Goto, Atsushi Mitsuhashi, Takuya Kuramoto, Sho Tabata, Sawaka Yukishige, Masaki Hanibuchi, Soji Kakiuchi, Atsuro Saijo, Yoshinori Aono, Hisanori Uehara, Seiji Yano, Julie G. Ledford, Saburo Sone, Yasuhiko Nishioka
Organizer
ATS 2013 Conference
Place of Presentation
Pennsylvania Convention Center (U.S.A.)
Related Report
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