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Peptides targeting EGFL7, a critical player in angiogenesis


Epidermal growth factor-like 7 (EGFL7) is an endothelial cell secreted protein whose expression is restricted to actively remodeling vascular endothelium. It is critical for vascular tube formation during angiogenesis through localizing to the extracellular matrix (ECM) at the basal surface of endothelial cells and promoting endothelial cell adhesion. In adults, expression of EGFL7 is detected only at sites of active angiogenesis during wound repair, in the pregnant uterus and in tumors. Over-expression of EGFL7 in many cancer types correlates with increased metastasis and poor prognosis. As a tumor grows beyond 1mm it recruits new blood vessels through the process of angiogenesis; suppressing this process to prevent further tumor growth and metastasis is a promising therapeutic strategy for cancer. Further, while the majority of current non-invasive vascular imaging approaches estimate only microvessel density, it is the shape and size of microvessels produced in highly angiogenic tumors that is predictive of cancer-specific mortality after adjusting for clinical factors. Consequently, angiogenesis is emerging as an important biomarker and therapeutic target in cancer.

Description of the Invention:

A suite of 9 novel peptides has been developed that specifically target and bind with high affinity to EGFL7 to inhibit its activity. The peptides have demonstrated significant anti-angiogenic activity by dramatically inhibiting human endothelial cell sprouting and tube formation, and the formation of tumor induced new blood vessels both in vitro and in vivo (mice). The peptides have also been conjugated to imaging agents such Gallium-68 for PET/CT imaging and demonstrated to bind with specificity and high affinity to EGFL7. The peptides hold significant promise for anti-angiogenesis therapies including for cancer, diabetic retinopathy and wet AMD. They also hold promise for development as angiogenesis imaging agents using nuclear imaging techniques for both research and for clinical applications such as clinical prognosis and monitoring of anti-angiogenesis treatments.

Potential Advantages/Applications:

• Potent in vivo angiogenesis inhibitors useful for treatment of cancer, diabetic retinopathy, wet AMD
• Novel composition of matter high affinity peptides with optimized serum half-life
• Potential combination anti-angiogenesis therapy with VEGF inhibitors
• Incorporation of the peptides on clinical nanoparticles can target drugs to sites of pathological angiogenesis
• Gallium-68 labeled peptides efficiently image angiogenesis for research or clinical applications.

Patent Information:


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