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Programmable half-life and anti-tumour effects of bispecific T-cell engager-albumin fusions with tuned FcRn affinity

Commun Biol. 2021-03; 
Ole A Mandrup, Sui Ching Ong, Simon Lykkemark, Anders Dinesen, Imke Rudnik-Jansen, Niels Frederik Dagnæs-Hansen, Jan Terje Andersen, Luis Alvarez-Vallina, Kenneth A Howard
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Catalog Antibody … rabbit anti-camelid VHH antibody (Genscript, # A01860) diluted 1:1000 in PBS for the Albu-LiTE fusion proteins. Coated plates were blocked for 1 h with 2% casein blocking buffer (… Get A Quote

摘要

Fc-less bispecific T-cell engagers have reached the immuno-oncology market but necessitate continual infusion due to rapid clearance from the circulation. This work introduces a programmable serum half-life extension platform based on fusion of human albumin sequences engineered with either null (NB), wild type (WT) or high binding (HB) FcRn affinity combined with a bispecific T-cell engager. We demonstrate in a humanised FcRn/albumin double transgenic mouse model (AlbuMus) the ability to tune half-life based on the albumin sequence fused with a BiTE-like bispecific (anti-EGFR nanobody x anti-CD3 scFv) light T-cell engager (LiTE) construct [(t 0.6 h (Fc-less LiTE), t 19 hours (Albu-LiTE-NB), t 26 hours (A... More

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