Hinge-deficient IgG1 Fc fusion: Application to human lactoferrin
作者： Yuki Shiga , Daisuke Murata , Akinori Sugimoto , Yuta Oshima , Minoru Tada
DOI: 10.1021/ACS.MOLPHARMACEUT.7B00221
关键词:
摘要: Fusion of therapeutic proteins with the antibody Fc domain is a strategy widely applied to increase protein half-life in plasma. In our previous study, we generated recombinant human lactoferrin (hLF)-immunoglobulin G1 fusion (hLF-hinge-CH2-CH3) improved stability, biological activity, and pharmacokinetics (Shiga, Y. et al. Eur J Pharm Sci., 2015, 67, 136––143). However, can potentially induce antibody-dependent complement-dependent cytotoxicity serious side effects. To overcome these drawbacks, engineered an hLF-Fc (hLF-CH2-CH3) without hinge region which essential for engaging receptors on immune cells inducing complement-mediated cell lysis. The hLF-CH2-CH3 was stably expressed Chinese hamster ovary (CHO) DG44 compared vitro activities, thermal pharmacokinetics, attenuation Fc-mediated effector functions conventional hinge-containing prote...
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