anti-5T4/exatecan antibody-drug conjugate TUB-030

An antibody-drug conjugate (ADC) composed of a Fc-silenced, humanized, immunoglobulin G1 (IgG1) monoclonal antibody directed against the oncofetal antigen 5T4 and site-specifically conjugated, via a cleavable linker, to the cytotoxic agent and DNA topoisomerase I inhibitor exatecan, with potential antineoplastic activity. Upon administration of anti-5T4/exatecan ADC TUB-030, the anti-5T4 antibody moiety selectively targets and binds to cells expressing 5T4. After internalization and cleavage within the tumor cell, exatecan is released and inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in DNA damage, cell cycle arrest and apoptosis in tumor cells overexpressing 5T4. In addition, TUB-030 induces a bystander effect, thereby killing neighboring tumor cells that don't necessarily express 5T4 in the tumor environment (TME). 5T4, a transmembrane glycoprotein, is overexpressed by a variety of cancer cell types while its expression is limited in normal adult tissues; its expression is correlated with increased invasiveness.