Targeting of Epithelial Cell Adhesion Molecule-Expressing Malignant Tumors Using an Albumin-Binding Domain-Fused Designed Ankyrin Repeat Protein: Effect of the Molecular Architecture.

ABSTRACT: Designed ankyrin repeat protein (DARPin) Ec1, a small scaffold protein (18 kDa), binds with high affinity the epithelial cell adhesion molecule (EpCAM) that is overexpressed in several carcinomas. To enhance the targeted delivery of cytotoxic drugs using Ec1, we investigated the potential of fusing Ec1 with an albumin-binding domain (ABD) to improve its circulation time and decrease renal uptake. Two fusion proteins were created, Ec1-ABD, with the ABD at the C-terminus, and ABD-Ec1, with the ABD at the N-terminus. Both variants were labeled with ¹¹¹In. ABD-fused variants bound specifically to EpCAM-expressing cells with picomolar affinity. Adding human albumin reduced the affinity. This effect was more pronounced for Ec1-ABD; however, the affinity remained in the subnanomolar ra

SUBMITTER: Tolmachev V 

PROVIDER: S-EPMC12154114 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature