anti-uPARAP ADC ADCE-D01

An antibody-drug conjugate (ADC) composed of AB-004, a humanized monoclonal antibody directed against urokinase plasminogen activator receptor-associated protein (uPARAP; endocytic receptor 180; Endo180; C-type mannose receptor 2) conjugated, via a protease-cleavable tetra-peptide linker, to the topoisomerase-1 inhibitor (TOP1i) P1021, with potential antineoplastic activity. Upon administration of anti-uPARAP ADC ADCE-D01, AB-004 targets and binds to uPARAP-expressing tumor cells. Upon binding, internalization and linker cleavage, P1021 is released, and inhibits DNA topoisomerase-1 activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of uPARAP-expressing tumor cells. uPARAP, a recycling endocytic receptor involved in collagen homeostasis and turnover, is overexpressed on various tumor cell types while its expression is limited in healthy tissues.