Definition

An antibody-drug conjugate (ADC) composed of a human monoclonal antibody targeting folate receptor alpha (FRa; FolRa; FOLR1) conjugated, via a cleavable hydrophilic linker, to the camptothecin analog and topoisomerase 1 inhibitor exatecan, with potential antineoplastic activity. Upon administration of anti-FRalpha/exatecan ADC PRO1184, the antibody moiety targets and binds to FRa expressed on tumor cells. Upon binding, cellular uptake and linker cleavage, exatecan is released. Exatecan inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and generating DNA single- and double-strand breaks, and leading to cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of FRa-expressing tumor cells. FRa is a glycosylphosphatidylinositol linked cell-surface glycoprotein that is widely expressed in certain cancers while its expression is limited in normal tissues.