Definition

An immunoconjugate consisting of a humanized monoclonal antibody directed against the tumor-associated antigen (TAA) disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) that is site-specifically conjugated, via a stable tri-peptide cleavable linker, to DM21, a cytotoxic maytansinoid microtubule-disrupting payload, with potential antineoplastic activity. Upon administration of anti-ADAM9 ADC IMGC936, the anti-ADAM9 monoclonal antibody moiety targets and binds to ADAM9 on tumor cells. Upon internalization, the maytansinoid moiety is released, binding to tubulin and disrupting microtubule assembly/disassembly dynamics, which may result in the inhibition of cell division and cell growth of tumor cells. ADAM9, belonging to the disintegrin and metalloproteinase (ADAM) family of proteases, plays a key role in cytokine and growth factor shedding and cell migration. It is overexpressed on multiple solid tumors while minimally expressed on normal tissue. Dysregulation of ADAM9 has been implicated in tumor progression, migration and metastasis. Its expression is correlated with poor prognosis. The antibody is engineered to include a YTE mutation to improve pharmacokinetics.