Production of recombinant human monoclonal antibody using ras-amplified BHK-21 cells in a protein-free medium

Biosci Biotechnol Biochem. 1996 May;60(5):811-7. doi: 10.1271/bbb.60.811.

Abstract

A ras oncogene-amplified recombinant BHK-21 cell line (ras-rBHK-IgG) has been established, and was shown to hyperproduce the recombinant IgG chimeric human monoclonal antibody (hMAb) AE6F4, which recognizes lung cancer cells. We found that the ras-rBHK-IgG cell could be easily cultured in a protein-free ERDF medium supplemented with iron(III) nitrate, hydroxyethyliminodiacetic acid, and non-protein synthetic attachment factor as well as in a serum-free ERDF medium supplemented with insulin, transferrin, ethanolamine, and sodium selenite. The productivity of recombinant hMAb from the cells cultured in dishes at high cell densities was higher in protein-free medium than in serum-containing medium. True high density culture of the ras-rBHK-IgG cells was done in protein-free medium using the Tecnomouse, which is a novel hollow fiber bioreactor system. After culture for 30 days in protein-free culture, a total amount of about 14 mg of the recombinant hMAb AE6F4 was obtained, and was shown to be reactive against lung cancer cells in tissues.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / biosynthesis*
  • Antibodies, Monoclonal / genetics
  • CHO Cells
  • Cell Line, Transformed
  • Cells, Cultured
  • Chelating Agents / pharmacology
  • Cricetinae
  • Cricetulus
  • Culture Media, Serum-Free
  • Ethanolamine
  • Ethanolamines / pharmacology
  • Ferric Compounds / pharmacology
  • Humans
  • Imino Acids / pharmacology
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / genetics
  • Insulin / pharmacology
  • Methacrylates / chemical synthesis
  • Methacrylates / pharmacology
  • Nitrates / pharmacology
  • Oncogene Protein p21(ras) / genetics*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Sodium Selenite / pharmacology
  • Transferrin / pharmacology

Substances

  • Antibodies, Monoclonal
  • Chelating Agents
  • Culture Media, Serum-Free
  • Ethanolamines
  • Ferric Compounds
  • Imino Acids
  • Immunoglobulin G
  • Insulin
  • Methacrylates
  • Nitrates
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Transferrin
  • Ethanolamine
  • N-(2-hydroxyethyl)iminodiacetic acid
  • Oncogene Protein p21(ras)
  • Sodium Selenite
  • ferric nitrate