Preclinical targeting of liver fibrosis with a Zr-labeled Fibrobody® directed against platelet derived growth factor receptor-β.

Purpose: Hepatic fibrosis develops as a response to chronic liver injury, resulting in the formation of fibrous scars. This process is initiated and driven by collagen-producing activated myofibroblasts which reportedly express high levels of platelet derived growth factor receptor-β (PDGFRβ). We therefore regard PDGFRβ as an anchor for diagnosis and therapy.

Single Domain Antibodies as Carriers for Intracellular Drug Delivery: A Proof of Principle Study.

Antibody-drug conjugates (ADCs) are currently used for the targeted delivery of drugs to diseased cells, but intracellular drug delivery and therefore efficacy may be suboptimal because of the large size, slow internalization and ineffective intracellular trafficking of the antibody. Using a phage display method selecting internalizing phages only, we developed internalizing single domain antibodies (sdAbs) with high binding affinity to rat PDGFRβ, a receptor involved in different types of diseases. We demonstrate that these constructs have different characteristics with respect to internalization rates but all traffic to lysosomes.

Mechanism of action of 4-substituted phenols to induce vitiligo and antimelanoma immunity.

Monobenzone is a 4-substituted phenol that can induce vitiligo and antimelanoma immunity. We investigated the influence of the chemical structure on the biological activity of a series of structurally related 4-substituted phenols. All phenols inhibited cellular melanin synthesis, and eight of ten phenols inhibited tyrosinase activity, using the MBTH assay.