Definition

An antibody-drug conjugate (ADC), consisting of mipasetamab, a humanized immunoglobulin (Ig) G1 monoclonal antibody directed against AXL receptor tyrosine kinase (AXL; UFO) that is site-specifically conjugated to uzoptitine (PL1601), which contains a valine-alanine cleavable linker and SG3199, a cytotoxic pyrrolobenzodiazepine (PBD) dimer, with potential antineoplastic activity. Upon administration of mipasetamab uzoptirine, mipasetamab binds to AXL, which is expressed on the surfaces of a variety of cancer cell types. Upon endocytosis and enzymatic cleavage, SG3199 is released and forms highly cytotoxic DNA interstrand cross-links, thereby blocking cell division and killing AXL-expressing cancer cells. AXL, a member of the TAM (TYRO3, AXL and MER) family of receptor tyrosine kinases, is overexpressed by many tumor cell types, and plays a key role in tumor cell proliferation, survival, invasion and metastasis; its expression is associated with drug resistance and poor prognosis.