Development of novel molecular-targeted therapy by humanized anti-CD26 monoclonal antibody in refractory osteolytic bone metastasis
| Project/Area Number |
25430157
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Taketo 埼玉医科大学, 医学部, 教授 (60230463)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | CD26 / 破骨細胞 / 破骨前駆細胞 / ヒト化抗CD26モノクローナル抗体 / p38MAPK / mi/Mitf / 骨吸収 / 溶骨性骨転移 / モノクローナル抗体 / TRAP / 溶骨性骨腫瘍 / 多発性骨髄腫 / 血管内皮細胞 / p38 MAPK / 血液内科 |
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| Outline of Final Research Achievements |
CD26 is expressed on normal human osteoclasts (OCs) and is intensely expressed on activated OCs in osteolytic bone tumors. M-CSF and sRANKL induced human OC differentiation in association with CD26 expression on monocyte-macrophage lineage cells. CD26 expression was accompanied by increased phosphorylation of p38 MAPK, which was crucial for early human OC differentiation. Humanized anti-CD26 monoclonal antibody, huCD26mAb, dose-dependently impaired the formation and function of TRAP/CD26 positive multi-nucleated OCs. It was revealed that huCD26mAb inhibited early OC differentiation via the inactivation of MKK3/6, p38 MAPK in the cytoplasm and subsequent dephosphorylation of mi/Mitf in the nucleus of human OC precursor cells, immediately after RANKL bound to RANK. However, it did not directly inhibit mature OCs. Our results suggest that targeting human OC precursor cells with huCD26mAb may have therapeutic potential for the treatment of osteolytic tumors to reduce bone destruction.
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Report
(4 results)
Research Products
(20 results)
