Definition

An bicycle toxin conjugate (BTC) composed of a synthetic, bicyclic peptide targeting the cell adhesion molecule nectin-4 (PVRL4) and conjugated to the cytotoxic agent monomethyl auristatin E (MMAE), via an inert sarcosine spacer chain and a valine-citrulline cleavable linker, with potential antineoplastic activity. Upon administration, the bicyclic peptide moiety of Nectin-4-targeting bicyclic peptide/MMAE BT8009 selectively binds to nectin-4. After internalization and proteolytic cleavage by peptidases that are upregulated in the tumor microenvironment (TME), MMAE binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and induces apoptosis in nectin-4 overexpressing tumor cells. Nectin-4, a tumor associated antigen (TAA) belonging to the nectin family, is overexpressed in a variety of cancers, but has a restricted distribution in normal tissue. It is associated with poor disease prognosis.