Definition

An antibody-drug conjugate (ADC) composed of HuBa-1-3D, a humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against human delta-like 1 homolog protein (DLK-1; DLK1) and site-specifically conjugated to PL1601, which contains a valine-alanine cleavable linker and SG3199, a cytotoxic pyrrolobenzodiazepine (PBD) dimer, with potential antineoplastic activity. Upon administration of anti-DLK-1 ADC ADCT-701, the antibody moiety targets and binds to DLK-1, which is expressed on the surfaces of a variety of cancer cell types. Upon endocytosis and enzymatic cleavage by cathepsin, free PBD is released and forms highly cytotoxic DNA interstrand cross-links, thereby blocking cell division and killing DLK-1-expressing cancer cells. DLK-1, an epidermal growth factor (EGF)-like membrane bound protein overexpressed by certain tumor cell types and on certain cancer stem cells (CSCs), plays a key role in tumor cell proliferation. Its expression is widely expressed during fetal development but in adult healthy tissue it is very restricted.