Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex

Kolumam G, et al., 2(7):730-43, EBioMedicine, 2015

This article describes generation of a humanized antibody named bFKB1 with the ability to activate fibroblast growth factor receptor 1 (FGFR1)/βKlotho (KLB) complex both in vitro as well as in vivo. Activation of this molecule in mice induced energy expenditure in brown adipose tissue (BAT), weight loss, and improvements in obesity related metabolic ailments. Phage derived antibodies were isolated and characterized for their interaction with the complexes FGFR1-KLB-bFKB1 and bFKB1-KLB-FGF using SPR and BLI technologies, respectively. An Octet RED system equipped with amine reactive biosensor tips allowed bFKB1 immobilization. Alternatively, KLB-ECD captured using the same biosensor tips were analyzed against human FGF21. This approach is expected to be a useful tool for the treatment of type2 diabetes and obesity related disorders.

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