Definition

An antibody-drug conjugate (ADC) composed of a human monoclonal antibody directed against the tumor-associated antigen (TAA) receptor tyrosine kinase-like orphan receptor 1 (ROR1) that is site-specifically conjugated with a tumor-cleavable beta-glucuronide linker to a tumor-cleavable prodrug of pyrrolobenzodiazepine (PBD) dimer, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of anti-ROR1 ADC CS5001 targets and binds to ROR1 expressed on tumor cells. Upon binding and internalization, both the linker and prodrug are selectively cleaved by lysosomal b-glucuronidase overexpressed in tumor cells. Free PBD is released and forms highly cytotoxic DNA interstrand cross-links, thereby blocking cell division and killing ROR1-expressing cancer cells. ROR1, also known as neurotrophic tyrosine kinase, receptor-related 1 (NTRKR1), is expressed during embryogenesis and in various hematological and solid malignancies. It plays key roles in tumor cell proliferation and survival.