title: Selection and characterization of high affinity VEGFR1 antibodies from a novel human binary code scFv phage library.
abstract: VEGFR1 is a receptor tyrosine kinase that has been implicated in cancer pathogenesis. It is upregulated in angiogenic endothelial cells and expressed on human tumor cells as well. VEGFR1 positive hematopoietic progenitor cells home to sites of distant metastases prior to the arrival of the tumor cells thus establishing a pre-metastatic niche. To discover high affinity human antibodies selective for VEGFR1 molecular imaging or for molecularly targeted therapy, a novel phage display scFv library was assembled and characterized. The library was constructed from the humanized 4D5 framework that was mostly comprised tyrosine and serine residues in four complimentary determining regions (CDRs). The library produced diverse and functional antibodies against a panel of proteins, some of which are of biomedical interest including, CD44, VEGFA, and VEGFR1. After panning, these antibodies had affinity strong enough for molecular imaging or targeted drug delivery without the need for affinity maturation. One of the anti-VEGFR1 scFvs recognized its cognate receptor and was selective for the VEGFR1.
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15219.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT, 06520.
authors.forename: Hye-Yeong
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15219.
authors.forename: Brendon
authors.initials: B
authors.lastname: Wahlberg
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15219.
authors.forename: W Barry
authors.initials: WB
authors.lastname: Edwards
keywords: VEGFR1; binary code; phage display; phage library; scFv