anti-KAAG1 antibody-drug conjugate ADCT-901

An antibody-drug conjugate (ADC) composed of 3A4, a humanized monoclonal antibody directed against human kidney associated antigen 1 (KAAG1; RU2) and conjugated, through a cathepsin-cleavable linker, to SG3199, a cytotoxic pyrrolobenzodiazepine (PBD) dimer, with potential antineoplastic activity. Upon administration of anti-KAAG1 ADC ADCT-901, the 3A4 moiety targets and binds to KAAG1, 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 KAAG1-expressing cancer cells. KAAG1, overexpressed by certain tumor cell types, plays a key role in tumor cell proliferation. Its expression on healthy tissue is very restricted.