In vivo evaluation of a novel format of a bivalent HER3-targeting and albumin-binding therapeutic affibody construct.

ABSTRACT: 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 ¹¹¹

SUBMITTER: Bass TZ 

PROVIDER: S-EPMC5322329 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature