title: Characterization of In Vivo Selected Bacteriophage for the Development of Novel Tumor-Targeting Agents with Specific Pharmacokinetics and Imaging Applications.
abstract: Bacteriophage (phage) display technology is a powerful strategy for the identification of peptide-based tumor targeting agents for drug discovery. Phage selections performed in vitro often result in many phage clones/peptides with similar properties and often similar sequence. However, these phage and corresponding peptides are selected, validated, and characterized outside the complicated milieu of a living animal. Thus, there is no guarantee that peptides from in vitro selections will successfully meet the requirements of an in vivo targeting compound. In comparison, in vivo phage display selections have the distinct advantage of identifying phage clones with robust pharmacokinetics and tumor/tissue targeting ability. This capacity has allowed for the identification of peptides with specific in vivo localization and/or clearance profiles. However, in vivo phage display selections also have the potential to result in an array of phage clones with various and unknown targets and little to no sequence similarity. Given these shortcomings, we have developed methods to select phage peptide display libraries in living mice to identify phage (and corresponding synthesized peptides) with specific clearance and/or tumor-targeting propensity. Additionally, we describe the use of labeled phage clones for the efficient screening of selected phage/peptides to aid in the identification and characterization of a phage clone with an optimal and specific pharmacokinetic profile.
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Newton-Northup
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, 65211, USA. deutschers@missouri.edu.|Harry S. Truman Veterans Memorial Hospital, Rm117 Schweitzer Hall, Columbia, MO, USA. deutschers@missouri.edu.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Deutscher
mesh_terms: D000588:Amines / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics*; D001435:Bacteriophages; D045744:Cell Line, Tumor; D061505:Cell Surface Display Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D057054:Molecular Imaging / Q000379:methods*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D061848:Optical Imaging / Q000379:methods; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D000072098:Single Photon Emission Computed Tomography Computed Tomography; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D010455:Peptides
keywords: Antigen discovery; Bacteriophage; Characterization/target validation; E. coli K 91 BluKan; Peptide-based tumor targeting; Pharmacokinetics; Screening; fUSE5