Development and in vitro validation of anti-mesothelin biobodies that prevent CA125/Mesothelin-dependent cell attachment.
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.
Bergan
Lindsay
L
Molecular Diagnositics Program, Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Gross
Jennifer A
JA
Nevin
Barry
B
Urban
Nicole
N
Scholler
Nathalie
N
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D001681:Biological Assay; D018394:CA-125 Antigen / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects*; D004171:Diploidy; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D058851:GPI-Linked Proteins; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D000090204:Mesothelin; D008969:Molecular Sequence Data; D010534:Peritoneal Neoplasms / Q000517:prevention & control* / Q000556:secondary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018394:CA-125 Antigen; D058851:GPI-Linked Proteins; D007135:Immunoglobulin Variable Region; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D000090204:Mesothelin