Selection and characterization of high affinity VEGFR1 antibodies from a novel human binary code scFv phage library

• VEGFR1 contributes to the pathogenesis cancer.
• To obtain VEGFR1 specific antibodies, a phage displayed scFv library was constructed.
• Four complimentarity determining regions were principally comprised of tyrosine and serine.
• High affinity antibody fragments were isolated and characterized.
• This is the first human antibody fragment specific for VEGFR1 from a phage displayed library.

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 complimentarity 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.