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

ABSTRACT: 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_½ 0.6 h (Fc-less LiTE), t_½ 19 hours (Albu-LiTE-NB), t_½ 26 hours (Albu-LiTE-WT), t_½ 37 hours (Albu-LiTE-HB

SUBMITTER: Mandrup OA 

PROVIDER: S-EPMC7940400 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature