Preparation of mouse-human chimeric antibody to an embryonic carbohydrate antigen, Lewis Y

J Biochem. 1993 Jan;113(1):114-7. doi: 10.1093/oxfordjournals.jbchem.a123993.

Abstract

Stage-specific embryonic antigen-1 (SSEA-1) is a well-known carbohydrate antigen that is specifically expressed on the surface of cancer cells as well as embryonic cells. In this study, starting with a previously established hybridoma producing a monoclonal antibody (named H18A) to Lewis Y antigen, which is closely related to SSEA-1, we cloned genomic DNA encoding active variable regions both of heavy and light chains of the antibody. Sequence analysis showed that VH and V kappa genes of H18A were in the VH 7183 family and V kappa C1 family, respectively. A transfected cell line named HC-H18A-7 expressing a recombinant chimeric H18A composed of mouse-derived antigen-binding variable regions and human-derived constant regions was established. The chimeric H18A was purified to homogeneity and shown to bind purified Lewis Y antigen with the same dose-response curve as the original H18A. The chimeric H18A looks more promising for clinical application than the original mouse-derived H18A because its antigenicity is expected to be reduced.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / genetics
  • Antibodies / immunology*
  • Base Sequence
  • Carbohydrate Sequence
  • DNA / chemistry
  • Genes, Immunoglobulin
  • Genetic Vectors
  • Humans
  • Immunoglobulin Heavy Chains / chemistry
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Light Chains / chemistry
  • Immunoglobulin Light Chains / genetics
  • Lewis Blood Group Antigens / chemistry
  • Lewis Blood Group Antigens / immunology*
  • Lewis X Antigen / chemistry
  • Lewis X Antigen / immunology
  • Mice
  • Molecular Sequence Data
  • Plasmids
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Transfection

Substances

  • Antibodies
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Lewis Blood Group Antigens
  • Lewis X Antigen
  • Recombinant Fusion Proteins
  • DNA