The antibody-peptide fusion protein, AT-02, is an effective opsonin with pan-amyloid reactivity

Abstract In systemic amyloidosis, the progressive accumulation of amyloid fibrils along with extracellular matrix components causes organ dysfunction, reduced quality of life, and is often fatal. Currently, twenty different proteins have been identified in systemic amyloid fibrils. Therapeutic elimination of tissue amyloid may improve organ function and patient outcomes. Amyloid-reactive immunoglobulins capable of stimulating cell-mediated clearance of amyloid deposits represent promising therapeutic strategies. AT-02 (zamubafusp alfa) is an immunoglobulin-peptide fusion protein comprising a humanized IgG1 and a pan-amyloid reactive peptide, p5R. AT-02 binds two ubiquitous components of all amyloids, namely amyloid fibrils and highly sulfated heparan sulfate glycans. This fusion protein exhibits specific reactivity with many amyloid types, obviating the need for individualized immunoglobulins for therapy. We demonstrate that AT-02 is an effective opsonin for amyloid by enhancing phagocytosis of amyloid extracts and inducing complement fixation. These data suggest that pan-amyloid binding reagents may provide novel treatment options for amyloid removal.