anti-5T4 antibody-drug conjugate SYD1875

An antibody-drug conjugate (ADC) composed of a humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against the oncofetal antigen 5T4 and site-specifically conjugated to a duocarmycin-based linker-drug valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA), with potential antineoplastic activity. Upon administration, the antibody moiety of SYD1875 selectively binds to cells expressing the 5T4 oncofetal antigen. After internalization and cleavage within the tumor cell by proteases, the free and activated duocarmycin payload binds to the minor groove of DNA and alkylates adenine at the N3 position, which eventually leads to tumor cell apoptosis. 5T4, a transmembrane glycoprotein, is overexpressed by a variety of cancer cell types; its expression is correlated with increased invasiveness.