Webster C, Caram-Salas N, Haqqani A, Thom G, Brown L, Rennie K, Yogi A, Costain W, Brunette E, Stanimirovic D (2016) Brain penetration, target engagement, and disposition of the blood-brain barrier-crossing bispecific antibody antagonist of metabotropic glutamate receptor type 1. FASEB J 30:1927-1940. doi: 10.1096/fj.201500078 PMID: 26839377
Summary: To generate a BBB-transmigrating antibody that could be reformatted to full IgG, scientists started with the BBB-crossing llama single domain antibody FC5. Standard phage display protocols were used to isolate single-chain variable fragments (scFv) from the FC5-scFv library. 6His Mouse Monoclonal antibody (Cat. #AB-213) was used to assess cell binding of scFvs of FC5 using fluorescence microvolume assay technology. An scFv that competed with FC5 binding was selected for further testing. An antibody antagonist of the metabotropic glutamate receptor-1 was fused with this scFv antibody fragment (BBB-mGluR1) and tested in an in vitro BBB model. The resulting bispecific antibody retained selective mGluR1 binding and saw a 20-fold enhanced rate of transcytosis across the BBB compared to fusion with control antibody fragment. Intravenous injection of BBB-mGluR1 had analgesic properties in a rat model of persistent inflammatory pain.
Related Products: 6His Mouse Monoclonal (Cat. #AB-213)