Exploring therapeutic efficacy of B cell depletion-combined regulatory plasma cell transfer in PBC
Project/Area Number |
15K08982
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Gastroenterology
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Research Institution | Akita University |
Principal Investigator |
MORITOKI Yuki 秋田大学, 医学部附属病院, 特任講師 (90585522)
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Research Collaborator |
TSUNEYAMA koichi
KIKUCHI kentaro
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Project Period (FY) |
2015-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 原発性胆汁性胆管炎 / B細胞除去療法 / 抗治療薬抗体 / ヒトCD20 / マウス / 抗CD20抗体 / PBC |
Outline of Final Research Achievements |
A novel biologics drug, anti-human CD20 humanized monoclonal antibody coined TKM-011 has been considered to be used in a clinical development for B cell depletion therapy in patients with primary biliary cholangitis (PBC). In parallel, human CD20 and FcγR expressing PBC model mice has been developed to examine therapeutic efficacy of B cell depletion using TKM-011. Human CD20 and FcγR hemi-expressing PBC model mice treated with TKM-011 exhibited B cell depletion as well as improvement of PBC pathological condition. In addition, development of anti-drug antibodies (ADA) against TKM-011 impaired B cell depletion as well as improvement of PBC liver pathology, suggesting lower possibility of ADA development would be preferred in PBC treatment using biologics.
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Academic Significance and Societal Importance of the Research Achievements |
PBC治療において、国内承認薬はウルソデオキシコール酸のみであり、効果不十分例ではベザフィブレートが追加投与される場合があるが、それでも効果不十分の場合には門脈圧亢進症、肝不全への進行を抑える有効な治療法はなく、肝移植が唯一の治療手段となることから、胆管炎を軽減し肝硬変への進行抑制可能な新規治療法が求められている。数年前より欧米ではオベチコール酸が新規承認となっているが、痒み等の有害事象報告や治療継続困難例も見られ、国内臨床開発は見送られている。本研究では、TKM-011によるPBC治療有効性が示唆されており、B細胞除去療法の臨床開発が更に進展することを期待したい。
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] Anti-drug Antibodies Against a Novel Humanized Anti-CD20 Antibody Impair Its Therapeutic Effect on Primary Biliary Cholangitis in Human CD20- and FcγR-Expressing Mice2018
Author(s)
Moritoki Y, Tsuneyama K, Nakamura Y, Kikuchi K, Shiota A, Ohsugi Y, Lian ZX, Zhang W, Yang GX, Ueki S, Takeda M, Omokawa A, Saga T, Saga A, Watanabe D, Miura M, Ueno Y, Leung PSC, Tanaka A, Gershwin ME, Hirokawa M.
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Journal Title
Frontiers in Immunology
Volume: 9
Pages: 2534-2534
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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