A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments

Nat Biotechnol. 1999 Mar;17(3):276-81. doi: 10.1038/7023.

Abstract

A single-chain Fv antibody fragment specific for the tumor-associated Ep-CAM molecule was isolated from a semisynthetic phage display library and converted into an intact, fully human IgG1 monoclonal antibody (huMab). The purified huMab had an affinity of 5 nM and effectively mediated tumor cell killing in in vitro and in vivo assays. These experiments show that nonimmunized phage antibody display libraries can be used to obtain high-affinity, functional, and clinically applicable huMabs directed against a tumor-associated antigen.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, Neoplasm / immunology*
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / therapeutic use
  • Bacteriophages / genetics
  • Blotting, Western
  • Cell Adhesion Molecules / immunology*
  • Cell Count
  • Colonic Neoplasms / drug therapy*
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Epithelial Cell Adhesion Molecule
  • Flow Cytometry
  • Gene Library
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Humans
  • Immunoglobulin Fragments / chemistry*
  • Immunohistochemistry
  • Leukocytes, Mononuclear / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Biology / methods*
  • Neutrophils / drug effects
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / therapeutic use
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Cell Adhesion Molecules
  • Epithelial Cell Adhesion Molecule
  • Immunoglobulin Fragments
  • Recombinant Proteins
  • immunoglobulin Fv
  • Granulocyte Colony-Stimulating Factor