anti-NaPi2b/exatecan antibody-drug conjugate TUB-040

An antibody-drug conjugate (ADC) composed of a Fc-silenced, humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against human sodium-dependent phosphate transport protein 2B (SLC34A2; NaPi2b), conjugated, via a cleavable linker, to the camptothecin analog and topoisomerase 1 inhibitor exatecan, with potential antineoplastic activity. Upon administration of anti-NaPi2b/exatecan ADC TUB-040, the antibody moiety targets and binds to NaPi2b 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. This leads to cell cycle arrest and tumor cell apoptosis. In addition, ADC TUB-040 is able to induce a bystander effect on neighboring tumor cells. This inhibits the proliferation of NaPi2b-expressing tumor cells. NaPi2b, a tumor-associated antigen (TAA), is overexpressed on a variety of cancer cells and plays a key role in the transport of inorganic phosphate (Pi) and the maintenance of phosphate homeostasis.