Genetic engineering of antibody molecules

Abstract

Antibodies are proteins produced by the immune system to combat pathogens and have long been appreciated for their exquisite specificity. The development of the hybridoma technology made it possible to immortalize single B-cells resulting in the production of unlimited quantities of antibodies of a single, well-defined antigen-binding specificity, known as monoclonal antibodies. However, the initial hybridoma-derived monoclonal antibodies were murine and highly immunogenic in people. Advances in genetic engineering and expression systems have been used to overcome the problem of the immunogenicity of rodent-produced antibodies and to improve the ability of the antibodies to trigger human immune effector activity. The development of chimeric, humanized, and totally human antibodies as well as antibodies with novel structures and functional properties has further expanded the potential use of monoclonal antibodies for targeted therapeutics. As a consequence, recombinant antibody-based therapies are now used to treat a variety of diverse conditions that include infectious diseases, inflammatory disorders, and cancer and today are one of the fastest growing classes of biopharmaceutical therapeutics. This article summarizes and compares different strategies for developing recombinant antibodies and their derivatives.