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drug_type
RELEVANT_DRUG
intervention_type
Drug
drug_description
An antibody–drug conjugate targeting tissue factor (TF/CD142) with a human IgG1 linked to the cytotoxic payload monomethyl auristatin E (MMAE). Upon binding TF, it is internalized and releases MMAE to inhibit microtubules, causing G2/M arrest and apoptosis; may also engage Fc-mediated effector functions.
nci_thesaurus_concept_id
C113164
nci_thesaurus_preferred_term
Tisotumab Vedotin
nci_thesaurus_definition
An antibody-drug conjugate (ADC) comprised of tisotumab, a monoclonal antibody against human tissue factor (TF) covalently coupled, via a protease-cleavable peptide linker, to monomethyl auristatin E (MMAE), an auristatin derivative and potent microtubule disrupting agent, with potential antiangiogenic, anticoagulant and antineoplastic activities. Upon administration of tisotumab vedotin, the tisotumab moiety binds to cell surface TF and is internalized. Tisotumab binds to factor VIIa (FVIIa), which interferes with the activation of factor X (FX) into FXa. This may prevent thrombin formation and cancer-associated venous thromboembolism, and may inhibit angiogenesis and tumor cell proliferation. After internalization of the agent, the MMAE moiety is released by proteolytic cleavage. It then binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and apoptosis. TF, a transmembrane protein and initiator of the coagulation cascade, is overexpressed in many tumor cells and tumor-resident endothelial cells. Expression of TF is correlated with metastasis, angiogenesis, tumor cell growth and tumor-associated thrombosis.
drug_mesh_term
tisotumab vedotin
drug_category
ANTIBODY DRUG CONJUGATE
drug_class
Conjugate
drug_delivery_route
Intravenous
drug_mechanism_of_action
Anti–tissue factor (TF/CD142) IgG1 linked via a protease-cleavable linker to monomethyl auristatin E (MMAE). After TF binding and internalization, MMAE is released to inhibit tubulin polymerization, inducing G2/M arrest and apoptosis; may also engage Fc-mediated effector functions and modestly interfere with TF/FVIIa signaling.
drug_name
Tisotumab vedotin
nct_id_drug_ref
NCT05866354