Recombinant antibodies: alternative strategies for developing and manipulating murine-derived monoclonal antibodies

By Peterson, N.C.

Since the introduction of hybridoma technology 20 years ago, numerous monoclonal antibodies with specificity to cellular, bacterial, and viral proteins have been developed. Application of monoclonal antibodies in biomedical research has substantially contributed to our understanding of the structural and physiologic components of intra- and extracellular protein interactions. Monoclonal antibodies that target antigens specific to infective agents or tumor cells may also be used as therapeutic agents. Despite the versatility of these molecules, monoclonal antibody/hybridoma production is labor-intensive and requires the use of live animals. The fact that monoclonal antibodies are derived from animals limits their use as systemic therapeutic agents in humans. This can be attributed to the human anti-mouse antibody response that is mounted against these therapeutically administered foreign proteins. Recent advances in our understanding of immunoglobulin structure through three-dimensional studies--using nuclear magnetic resonance and X-ray crystallography and increased computer-assisted molecular modeling capabilities, combined with the application of recombinant approaches--has led to the evolution of a new class of antibody-like molecules or man-made antibodies. The potential of recombinant antibodies has been realized globally by academic and industrial institutions; the efficacy, toxicity, and pharmacokinetics of these antibody-derived compounds are being tested in a variety of animal models. This review summarizes various approaches for producing recombinant antibodies and discusses their potential as anti-cancer compounds so that those who are involved in relevant experimental animal protocols may gain a better understanding of this rapidly growing area. Additionally, by mimicking the affinity maturation of antibodies in vitro, phage display strategies have the potential to reduce or eliminate the use of animals in antibody production protocols.