Anti-Human Tissue Factor (TF) (Tisotumab) - 1.0 mg

All|Recombinant Antibodies>Biosimilar Recombinant Antibodies|Primary Monoclonal Antibodies

2 - 8°C Wet Ice

Tissue factor (TF; also known as thromboplastin, factor III, or CD142) is the primary initiator ofblood coagulation1. During coagulation, TF interacts with proteolytic cleavage factor VII togenerate activated FVII (FVIIa), which then forms a TF:FVIIa complex 22. This complex thenactivates coagulation factor X to generate FXa and ultimately leads to clot formation viathrombin. The coagulation cascade is initiated when a vessel wall is disrupted by injury or whenTF is upregulated on monocytes due to inflammation. In either circumstance, TF is exposed tocirculating FVII and FVIIa allowing clot formation to commence along with induction ofintracellular protease-activated receptor 2 (PAR-2) signaling. TF contributes to tumorprogression in a variety of cancers by exploiting both tissue factor procoagulant activity andPAR-2 signaling cascades. As such, TF is a target of cancer immunotherapy. GCT1015-04 (Tisotumab) was developed to target TF-expressing tumors for the treatment ofcervical and other cancers1, 2. Tisotumab delivers a toxic payload to tumor cells via its anti-TFhumanized monoclonal antibody (TF-011) conjugated to the microtubule-disrupting agentMMAE. TF-011 is conjugated with maleimidocaproyl-valine-citrulline-p-aminobenzoyl-monomethyl auristatin E (vcMMAE) on cysteine groups in the antibody hinge region. MMAEinitiates cell cycle arrest and apoptosis of both tumor and bystander cells upon delivery. Tisotumab induces immunogenic cell death as well as antibody-dependent cellular toxicity andantibody-dependent cellular phagocytosis1, 2. Tisotumab also inhibits TF from binding FVIIa, andthereby inhibits TF:FVIIa-induced ERK phosphorylation and IL-8 production. Thus, PAR-2dependent signaling is inhibited by the antigen-binding fragment. Tisotumab activity does notdisrupt normal coagulation. Tisotumab was generated by immunizing HuMAb mice with TF-ECDHis and/or TF-expressingNSO cells2. Hybridomas were generated from mice that showed TF-specific antibodies in serum.The immunoglobulin variable heavy and light chain regions were sequenced, and recombinantantibodies were generated. This non-therapeutic biosimilar antibody is not conjugated to MMAE and thus does not includethe drug payload.

≥ 5.0 mg/ml

TF is expressed on the surface of cells from a wide variety of organsincluding, the brain, heart, intestine, kidney, lung, placenta, uterus, and testes. Additionally, expression is found in subendothelial vessel walls, pericytes, and fibroblasts that are not in directcontact with blood. About 1-2% of monocytes also express TF. TF is aberrantly expressed byvarious cancers, including cervical, non-small cell lung, endometrial, prostate, ovarian, esophageal, and bladder.