Summary:

Scientists at the National Cancer Institute (NCI) have discovered a novel therapeutic, diagnostic and prognostic target for thrombosis: Soluble Tissue Factor (sTF). NCI has generated first-in-class antibodies and platform selectively neutralizing pathological coagulation while preserving normal hemostasis. This platform technology can be used to prevent, diagnose and treat pathological thrombosis caused by a variety of clinical conditions-including cancer, sepsis, infectious diseases (e.g., COVID), autoimmune disorders, trauma, heart conditions and inflammatory conditions. It offers a much more sensitive and specific test of thrombosis than the current D-dimer test. It may be applicable to any clinical condition which induces necroptosis, pyroptosis and NETosis, such as cancer, neurodegenerative disease, ischemia-reperfusion and acute injuries, traumatic injuries, bacterial and viral infections, cardiovascular conditions, and atherosclerosis, inflammatory, autoimmune conditions, and others.   

Description of Technology:

Investigators at the National Cancer Institute (NCI) have identified and therapeutically validated a distinctive, disease-restricted driver of thrombosis: soluble tissue factor (sTF). sTF is generated through proteolytic cleavage during inflammatory cell death.

Mechanistically, the researchers demonstrated that sTF generation is not limited to necroptosis but represents a conserved outcome of multiple inflammatory cell death pathways, including pyroptosis and NETtosis.

Pathological thrombosis remains a leading cause of morbidity and mortality in sepsis, cancer, autoimmune diseases, viral infections, and inflammatory disorders. Current anticoagulant and thrombosis treatments options such as Heparins and Warfarin are effective at reducing clot formation, but act indiscriminately on the coagulation cascade, disrupt normal hemostasis, and are associated with significant bleeding risk. Current thrombosis diagnostics, D-dimer, a fibrin degradation byproduct, is a late stage marker that lacks sensitivity. This invention provides an alternative for early detection based on sTF that is more sensitive and specific.

To selectively target this mechanism, the team developed novel humanized monoclonal antibodies (e.g., 58B3 and 56E5) that specifically recognize human soluble tissue factor (hsTF), but not full-length membrane-bound tissue factor (flTF). This selectivity preserves physiological hemostasis while inhibiting pathological coagulation.

In vivo validation using human samples of various clinical diseases demonstrated that administration of sTF-specific antibodies prevents fibrinogen depletion and reduces thrombin–antithrombin (TAT) complex elevation, effectively normalizing coagulation parameters. These results establish proof of concept that selective sTF neutralization can block pathological thrombosis without systemic anticoagulation.

By establishing sTF as a unifying mechanistic link between inflammatory cell death and thrombosis across sepsis, cancer, infection, autoimmune disease, cardiovascular disorders, and metabolic inflammation, this antibody platform represents a first-in-class strategy to selectively inhibit pathological coagulation while preserving normal hemostasis. The approach offers a safer, more precise therapeutic and diagnostic alternative to conventional anticoagulants.

The humanized monoclonal antibodies, as well as methods of using sTF as a target for diagnosis, treatment and prevention of thrombosis and associated diseases are available for licensing or collaborative development to advance clinical translation. Partnership opportunities include preclinical optimization, clinical development, and diagnostic assay co-development.

Potential Commercial Applications:

• Diagnostic tool for early detection and monitoring of sTF in plasma.Diagnostic tool for early detection and monitoring of thrombosis, much more sensitive and specific test than the currently used D-dimer test.
• Basis for diagnostic kits such as ELISA and point-of-care assays.
• Diagnostic tool for early detection of DVT and PE with radiolabeled anti-sTF antibody in combination with ultrasound /CT scan
• Therapeutic use for sepsis-associated thrombosis.
• Therapeutic use for cancer-associated thrombosis.
• Therapeutic use viral infection–associated thrombosis.
• Therapeutic use autoimmune disorders.
• Therapeutic use cardiovascular inflammatory diseases.
• Therapeutic use for acute lung injury including Acute Respiratory Distress Syndrome ARD.
• Therapeutic use for metabolic and vascular inflammatory diseases
• Therapeutic use for high efficient inhibition of thrombosis with anti-sTF-based bispecific antibodies.

Competitive Advantages:

• Selective targeting of pathological soluble tissue factor (sTF).
• Preservation of normal hemostasis.
• Potential for long-acting biologic prevention.
• Specific mechanism-based intervention tied to inflammatory cell death.