Tissue Factor (TF)

Class

Tissue Factor-directed antibody-drug conjugate (exatecan/topoisomerase I inhibitor payload)

Pathway

Antibody-mediated payload delivery causing DNA damage/apoptosis, plus bystander killing of TF-negative tumor cells

Tissue Factor (TF) is a transmembrane protein that normally sits on cells outside blood vessels, where it functions as the initiating receptor of the coagulation cascade: when vessel injury exposes it to circulating clotting factor VIIa, it triggers clot formation. Many solid tumors express TF at high levels on their cell surface, where it also contributes to tumor growth signaling and blood vessel formation. This combination of high, relatively tumor-restricted expression and the protein's propensity to be internalized after antibody binding makes TF an attractive docking site for antibody-drug conjugates (ADCs). In this approach, an antibody directed against TF is chemically linked to a cytotoxic payload, in this case a topoisomerase I inhibitor related to exatecan, which damages DNA and triggers cell death. After the antibody binds TF on the tumor cell surface, the complex is drawn inside the cell, releasing the payload intracellularly. Because the released payload can diffuse to and kill neighboring tumor cells regardless of their own TF expression, this mechanism can address the uneven, patchy target expression typical of solid tumors. This strategy is broadly relevant across TF-expressing solid tumors, particularly those with limited alternative targeted options.