Production of functional chimaeric mouse/human antibody

Nature. 1984 Dec;312(5995):643-6. doi: 10.1038/312643a0.

Abstract

The availability of monoclonal antibodies has revived interest in immunotherapy. The ability to influence an individual's immune state by administering immunoglobulin of the appropriate specificity may provide a powerful approach to disease control and prevention. Compared with immunoglobulin from other species, human immunoglobulin (Ig) might be best for such therapeutic intervention; it might function better with the recipient's effector cells and should itself be less immunogenic. The success of the mouse hybridoma system suggests that immunoglobulin of virtually any specificity can be obtained from a properly immunized animal. In the human system, however, immunization protocols are restricted by ethical considerations, and it is not yet clear whether human antibody-producing cell lines of the required specificity can be obtained from adventitiously immunized individuals or from in vitro immunized cells. A method which might circumvent these difficulties is to produce antibodies consisting of mouse variable regions joined to human constant regions. Therefore, we have constructed immunoglobulin genes in which the DNA segments encoding mouse variable regions specific for the hapten trinitrophenyl (TNP) are joined to segments encoding human mu and kappa constant regions. These 'chimaeric' genes are expressed as functional TNP-binding chimaeric IgM. We report here some of the properties of this novel IgM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / genetics*
  • Antibody Formation*
  • Cell Line
  • Chimera*
  • DNA Restriction Enzymes
  • Genes
  • Haptens
  • Humans
  • Hybridomas / immunology
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin M / genetics*
  • Mice

Substances

  • Antibodies, Monoclonal
  • Haptens
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin M
  • DNA Restriction Enzymes