administration plannning of antibody drugs based on PK/PD analysis

• Project/Area Number: 24790145
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Gunma University
• Principal Investigator: ARAKI TAKUYA 群馬大学, 医学(系)研究科(研究院), 准教授 (00568248)
• Research Collaborator: YAMAMOTO Koujirou ; NAGANO Daisuke ; NAKAMURA Hironori
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 抗体医薬 / 個別化医療 / 薬物療法 / 質量分析 / 成分分析 / 抗体医薬品 / 抗抗体医薬品抗体 / バイオマーカー / 二次無効

Outline of Final Research Achievements

Antibody drugs (ADs) show remarkable benefits, while resistance to AD or infusion reaction, which are associated with expression of anti-AD antibody, are often induced. In this study, we tried to develop simple process to establish the method for quantitation of unknown proteins and find factors of resistant to AD therapy.
Blank serum samples and serum spiked with ADs were reduced, alkylated and digested by trypsin and analyzed by LC-TOF MS. Several specific precursor ion peaks for AD were determined from total ion chromatogram data using principal component analysis (PCA). Then, those peaks were analyzed by LC-MS/MS. Using purified peak with SPE process, we could detect ADs in serum with sufficiently lower limit of quantification. Our method is applicable to analyze other ADs and unknown substances such as anti-AD antibody, because it does not require structural determination of target substance. Now we have been assessing factors affecting the efficacy of AD using clinical samples.

Research Products

• [Presentation] Establishment of method for quantitation of antibody drugs using LC-MS/MS with biomarker analytical technique (2014)
  • Author(s): Hironori Nakamura, Takuya Araki, Daisuke Nagano, Koujirou Yamamoto
  • Organizer: 6th International Conference on Advanced Micro‐Device Engineering
  • Place of Presentation: Kiryu, Gunma, Japan
  • Year and Date: 2014-12-05
• [Presentation] Quantification of an antibody drug, infliximab, in human blood using biomarker analysis technique (2014)
  • Author(s): Hironori Nakamura, Takuya Araki, Daisuke Nagano, Koujirou Yamamoto
  • Organizer: International Congress of Therapeutic Drug Monitoring & Clinical Toxicology European Conference
  • Place of Presentation: Prague, Czech Republic
  • Year and Date: 2014-08-28 – 2014-08-30
• [Presentation] LC-MS/MS method for the quantification of infliximab in human blood (2013)
  • Author(s): Hironori Nakamura, Takuya Araki, Tomonori Nakamura, Koujirou Yamamoto
  • Organizer: 13th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology (IATDMCT)
  • Place of Presentation: Salt Lake City, USA
• [Presentation] Development approach using LC-MS/MS and biomarker analytical technique for the quantification of infliximab in human blood (2013)
  • Author(s): Hironori Nakamura, Takuya Araki, Koujirou Yamamoto
  • Organizer: 第7回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 仙台
• [Presentation] Establishment of prediction method for clinical efficacy of antibody drugs using LC-MS/MS with biomarker searching technique
  • Author(s): Hironori Nakamura, Takuya Araki, Koujirou Yamamoto
  • Organizer: 5th InternationalConference on Advanced Micro‐Device Engineering
  • Place of Presentation: Kiryu, Gunma, Japan