Dr. Pasqualini will develop components of a virus that will be designed to kill neuroendocrine cancer cells. The virus will be modified to attach to somatostatin receptors on pancreatic neuroendocrine tumor cells, limiting negative effects on healthy tissues. Researchers will introduce a strategy for capitalizing on the overexpression of one such receptor, somatostatin receptor type 2 (SSTR2), in neuroendocrine tumors (NETs) of the pancreas. They will prepare phage-based gene delivery constructs targeted by a somatostatin peptide-analogue known to selectively bind SSTR2 in pancreatic NETs. The strategy utilizes a hybrid vector with genetic elements from adeno-associated virus (AAV) and an M13-derived phage, called AAVP, displaying somatostatin peptide-analogue to mediate selective internalization of the viral particles after systemic administration. Establishing AAVP for delivery of TNF-a (AAVP-TNF) would provide for the systemic, targeted delivery of an apoptotic agent directly to the vulnerable vasculature of pancreatic NETs with limited toxicity for normal tissues.
Smith TL, Yuan Z, Cardó-Vila M, et al. AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas. Proc Natl Acad Sci U S A. 2016;113(9):2466-71.