Development and in vitro validation of anti-mesothelin biobodies that prevent CA125/Mesothelin-dependent cell attachment

Cancer Lett. 2007 Oct 8;255(2):263-74. doi: 10.1016/j.canlet.2007.04.012. Epub 2007 Jun 7.

Abstract

Preventing peritoneal implantation of carcinoma cells could prolong ovarian cancer patient remission and survival. Peritoneal cells constitutively express mesothelin, a ligand for CA125 that is expressed by tumor cells. Thus blocking CA125/mesothelin-dependent cell attachment may prevent or delay peritoneal metastatic recurrence. We developed a high-throughput screening system for reagents able to block CA125/mesothelin-dependent cell attachment with a sensitive quantitative readout. Using a novel yeast-expression system to produce secreted, in vivo biotinylated proteins and biobodies (Bbs), we generated anti-mesothelin Bbs. Anti-mesothelin Bbs derived from high affinity yeast-display scFv detected both membrane-bound and soluble mesothelins and inhibited CA125/mesothelin-dependent cell attachment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / biosynthesis*
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / pharmacology*
  • Biological Assay
  • CA-125 Antigen / drug effects*
  • Cell Adhesion / drug effects*
  • Diploidy
  • Drug Screening Assays, Antitumor / methods
  • GPI-Linked Proteins
  • Humans
  • Immunoglobulin Variable Region / biosynthesis
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / pharmacology
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Molecular Sequence Data
  • Peritoneal Neoplasms / prevention & control*
  • Peritoneal Neoplasms / secondary
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism

Substances

  • Antibodies, Monoclonal
  • CA-125 Antigen
  • GPI-Linked Proteins
  • Immunoglobulin Variable Region
  • Membrane Glycoproteins
  • Recombinant Proteins
  • mesothelin