Summary:

The National Cancer Institute (NCI) seeks research co-development partners and/or licensees for a novel humanized monoclonal antibody (58B3) that selectively targets a newly identified soluble Tissue Factor (sTF) to diagnose, prevent and treat pathological thrombosis associated with inflammation, viral/bacterial infection, sepsis and cancer – without affecting normal hemostasis.

Description of Technology:

Thrombosis is a major clinical complication associated with inflammation, viral infection, sepsis and cancer. It remains a leading cause of morbidity and mortality worldwide. Current anticoagulant therapies, such as heparin, are effective at reducing clot formation but disrupt normal hemostasis, leading to significant risks of bleeding. A major challenge in the field has been the inability to selectively target pathological thrombosis without interfering with physiological blood clotting, which is critical for wound healing and vascular repair. Addressing this unmet need requires identification of disease-specific mediators that distinguish pathological coagulation from normal hemostasis.

Investigators at NCI have identified a novel functional soluble Tissue Factor (sTF), a proteolytically cleaved form of the membrane-bound full length Tissue Factor (flTF), as a key driver of pathological thrombosis. Unlike flTF, which maintains normal hemostasis, sTF is shed from macrophages during necroptosis and exhibits potent procoagulant activity, as shown in inflammation and viral infection models – including severe COVID-19. To selectively target this disease-associated protein, investigators developed a humanized rabbit monoclonal antibody, 58B3, that recognizes a neoepitope at the cleavage site of sTF. This antibody specifically blocks the coagulation activity of sTF without affecting flTF, thereby preventing pathological clotting while preserving normal hemostasis. In addition to its therapeutic potential, 58B3 can detect native sTF in human plasma, enabling its use as a novel diagnostic marker and risk predictor for thrombosis. As sTF is the initiator of coagulation cascade, targeting sTF by 58B3 can potentially prevent thrombosis in high-risk patients with these pathological conditions. 

This technology represents a first-in-class diagnostic, preventive, and therapeutic solution for pathological thrombosis. The humanized monoclonal antibody 58B3 is available for licensing or collaborative development to advance it toward clinical translation. Partnership opportunities include preclinical optimization, clinical development, and diagnostic assay co-development. Given its unique mechanism of selectively blocking sTF-driven coagulation, 58B3 offers significant advantages over current anticoagulants, positioning it as a transformative therapy for patients at high risk of thrombosis in most pathological settings – including inflammatory and infectious diseases.

Potential Commercial Applications:

• Therapeutic antibody for treating pathological thrombosis in infection, inflammation, cancer and sepsis
• Combination therapy with current anticoagulants to reduce bleeding risk
• Diagnostic tool for early detection of sTF in plasma
• Companion diagnostic for monitoring sTF and guiding treatment
• Basis for diagnostic kits such as ELISA or other point-of-care assays
• Prophylactic use in high-risk patients to prevent thrombosis
• Research reagent for studying sTF biology and validating drug targets

Competitive Advantages:

• Selectively targets sTF with high affinity without affecting full-length TF, preserving normal hemostasis
• Reduces risk of bleeding compared to standard anticoagulants; e.g., heparin, direct oral anticoagulants (DOACs)
• First-in-class therapeutic approach addressing a previously unrecognized driver of thrombosis
• Potential for early intervention by detecting and neutralizing sTF before clot formation
• Humanized monoclonal antibody format supports clinical translation and broad applicability
• Opportunity for combination use with existing anticoagulants to improve safety and efficacy