Definition

An antibody-drug conjugate (ADC) composed of sirtratumab, a monoclonal antibody directed against SLIT and NTRK-like protein 6 (SLITRK6), covalently linked to the cytotoxic agent monomethyl auristatin E (MMAE), an auristatin derivative and a potent inhibitor of microtubule polymerization, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of sirtratumab vedotin binds to SLITRK6 expressed on tumor cells, which facilitates both the internalization of the ADC and the intracellular delivery of MMAE. Upon cleavage, MMAE binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and tumor cell apoptosis. SLITRK6, a member of the Slitrk family of leucine-rich repeat (LRR) neuronal transmembrane proteins, is minimally expressed in normal tissue but overexpressed in a variety of cancers, including bladder cancer, some forms of lung cancer, breast cancer and glioblastoma.