Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody
作者: Simona CignettoChiara ModicaCristina ChiriacoLara FontaniPaola MillaPaolo MichieliPaolo M. ComoglioElisa Vigna
作者单位: 1Candiolo Cancer Institute, FPO-IRCCS, Str Prov 142, 10060 Candiolo, Italy
2University of Turin, Department of Oncology, Str Prov 142, 10060 Candiolo, Italy
3University of Turin, Department of Science and Drug Technology, Via P. Giuria 9, 10125 Turin, Italy
刊名: Molecular Oncology, 2016, Vol.10 (6), pp.938-948
来源数据库: Elsevier Journal
DOI: 10.1016/j.molonc.2016.03.004
关键词: Cancer targeted therapyMetAntibodyFabHalf-lifeProtein engineering
英文摘要: Abstract(#br)The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). The two newly engineered molecules showed biochemical properties comparable to the original MvDN30 in vitro , acting as full Met antagonists, impairing Met...
全文获取路径: Elsevier  (合作)
影响因子:6.701 (2012)

  • therapeutic 治疗的
  • potency 潜力
  • antibody 抗体
  • novel 长篇小说
  • improve 改进
  • strategy 战略
  • Domain 区域