SYSTEMIC RADIONUCLIDE THERAPY TARGETED TO VEGF RECEPTORS IN TUMOR VASCULATURE

The overall goal of this collaborative project between SibTech Inc PI Backer J and Johns Hopkins University PI Pomper M is clinical development of efficient and cost effective anti angiogenic Lu radiopharmaceutical scV Lu for VEGF receptor mediated targeting of angiogenic tumor vasculature Current very expensive anti angiogenic compounds induce transient regression of tumor vasculature in some patients but cause only marginal if any improvement in overall survival in many cancer patients Our data in mouse models of primary and metastatic breast cancer indicate that scV Lu induces a sustainable vascular regression inhibits growth of primary tumor and metastatic lesions improves overall survival and readily combines with front line chemotherapy scV is a proprietary recombinant single chain vascular endothelial growth factor scVEGF engineered for site specific derivatization with PEGylated chelators which binds to and internalized by VEGF receptors with native affinity In Phase I of this contract using syngeneic mouse model of orthotopic breast cancer we will establish if selective targeting of VEGFR or VEGFR with scV Lu may provide additional therapeutic benefits and define our lead candidate for further development In Phase II we will develop the lead scV Lu candidate through late preclinical development GMP production dosimetry toxicology and undertake physician initiated exploratory Phase I trial in cancer patients