Evaluation of a novel ¹⁷⁷Lu-labelled therapeutic Affibody molecule with a deimmunized ABD domain and improved biodistribution profile.

ABSTRACT:

Purpose

Fusion of Affibody molecules with an albumin-binding domain (ABD) provides targeting agents, which are suitable for radionuclide therapy. To facilitate clinical translation, the low immunogenic potential of such constructs with targeting properties conserved is required.

Methods

The HER2-targeting Affibody molecule ZHER2:2891 was fused with a deimmunized ABD variant and DOTA was conjugated to a unique C-terminal cysteine. The novel construct, PEP49989, was labelled with ¹⁷⁷Lu. Affinity, specificity, and in vivo targeting properties of [¹⁷⁷Lu]Lu-PEP49989 were characterised. Experimental therapy in mice with human HER2-expressing xenografts was evaluated.

Results

The maximum molar activity of 52 GBq/µmol [¹⁷⁷Lu]Lu-PEP49989 was ob

SUBMITTER: Liu Y 

PROVIDER: S-EPMC11527907 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature