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anti-FRalpha antibody-drug conjugate ZW191

An antibody-drug conjugate (ADC) composed of a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting folate receptor alpha (FRa; FolRa; FOLR1) conjugated, via a maleimidocaproyl (MC) anchor and a glycyl glycyl phenylalanyl glycine (GGFG)-aminomethyl (AM) protease-cleavable linker, to the camptothecin-based topoisomerase 1 inhibitor ZD06519, with potential antineoplastic activity. Upon administration of anti-FRalpha ADC ZW191, the antibody moiety targets and binds to FRa expressed on tumor cells. Upon binding, cellular uptake and linker cleavage, ZD06519 is released. ZD06519 inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and generating DNA single- and double-strand breaks. This leads to cell cycle arrest and tumor cell apoptosis. In addition, ZD06519 is able to induce a bystander effect on neighboring cells in the tumor environment. This inhibits the proliferation of 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.
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Synonym:anti-FRa ADC ZW191
anti-FRa/ZD06519 ADC ZW191
anti-FRalpha ADC ZW191
Code name:ZW 191
ZW-191
ZW191
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