Abstract

Our group originally developed two targeting platforms to uncover ligand-receptor interactions in disease: peptide and antibody library selection in vivo and in vitro. By using these complementary technologies, we probe the molecular diversity to discover cell surface addresses (termed ZIP codes) for delivery of therapeutics to selective vascular beds. In this lecture, the topics covered will be: (i) Human Vascular Mapping: We developed scientific and ethics frameworks for direct combinatorial screening in cancer patients and validated human tumor ZIP codes. We translated peptidomimetics into investigational new drugs (INDs), realized sequential selection in patients, and identified human ligand-receptors. (ii) Molecular-genetic Imaging: We invented AAV-phage (AAVP) for targeted transcription-based molecular imaging and created self-assembled nanotechnology-based phagenanogold networks. We are integrating these into nanoparticle-based delivery systems for several payloads, including siRNAs. (iii) Fingerprinting Antibodies: We “fingerprinted” auto-antibodies from cancer patients, thus discovering tumor antigens that serve as prognostic and diagnostic markers, in addition to receptors for ligand-directed delivery. (iv) Disease Models: We reverted obesity by targeting the vasculature of white fat for destruction. We also identified cancer ZIP codes, within multiple tumor compartments, including infiltrating bone-marrow derived cells and pericytes. (v) Small peptidomimetics & human antibodies: We developed biopanning methodologies in vivo and ex vivo, which yielded angiogenesis inhibitors and tumor-specific targets for imaging and radiosensitization.