Tumor-specific cytosol-penetrating antibodies for antigen- and TME-dependent intracellular cargo delivery.

ABSTRACT: Although a considerable number of disease-related biomolecular interactions occur in the cytosol, therapeutic and diagnostic application of target-specific binding proteins is largely confined to surface-exposed or extracellular targets. Therefore, protein-cargo delivery approaches, including cell-penetrating peptides and cytosol-penetrating antibodies, are being explored to overcome this limitation. In this context, we have developed a modular approach for cytosolic penetration of tumor cells based on bispecific antibodies containing a masked cytosol-penetrating Fab on one arm and a tumor-targeting scFv linked via an endosomal cleavable linker on the other arm. The relevance of the antigen-specific binding, internalization, and cytosolic cargo delivery was demonstrated in several in vi

SUBMITTER: Dombrowsky CS 

PROVIDER: S-EPMC11786873 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature