The objective of this contract is to develop INTI-1, an Anti-DEspR Therapeutic mAb and related Companion Diagnostic mAb, for use against DEspR+ cancers lacking effective therapies, such as Pancreatic Adenocarcinoma (PCa), Glioblastoma Multiforme (GBM) and Triple Negative Breast Cancer {TNBC}. Anti-DEspR mAbs have identified DEspR+ tumor cells (TCs), cancer stem cells (esCs) and tumor vascular endothelial cells (TVECs) in PCa, GBM and TNBC primary tumors and respective cell lines (Panc-1, U87, MDA-MB-231 and -468). DEspR represents a novel pathway contributing to tumor invasiveness, metastasis and angiogenesis. In preliminary studies, anti-DEspR therapy resulted in regression of spontaneous or induced mammary tumors in immunocompetent rodents and regression of human Panc-l and GBM US7 esC-derived xenograft tumors in nude rats in vivo, and inhibited human CSC survival, TC invasion and EC angiogenesis in vitro. The Phase I Objective is to evaluate the feasibility of using INTI-l as a therapeutic against DEspR+ human tumors.
