biostudies-literatureUnknown7Bass TZOverexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation. In vitro, 3A3 efficiently inhibited growth of HER3-expressing BxPC-3 cells. Biodistribution in mice was measured using 3A3 that was site-specifically labelled with ¹¹¹In via a DOTA chelator. The residence time of ¹¹¹Scientific reports43118https://www.ebi.ac.uk/biostudies/studies/S-EPMC5322329biostudies-literatureIn vivo evaluation of a novel format of a bivalent HER3-targeting and albumin-binding therapeutic affibody construct.PMC5322329Orlova AFrejd FYMitran BTolmachev VStahl SRosestedt MLofblom JBass TZfalseIn vivo evaluation of a novel format of a bivalent HER3-targeting and albumin-binding therapeutic affibody construct.Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation. In vitro, 3A3 efficiently inhibited growth of HER3-expressing BxPC-3 cells. Biodistribution in mice was measured using 3A3 that was site-specifically labelled with ¹¹¹In via a DOTA chelator. The residence time of ¹¹¹2017-01-01T00:00:00Z2017 Feb2026-05-30T06:57:07.393Z2019-03-27T02:37:10ZS-EPMC53223292823006510.1038/srep43118