Antibodies and gene therapy: teaching old 'magic bullets' new tricks

Abstract

The emergence of recombinant technologies has revolutionized the selection and production of monoclonal antibodies, allowing the design of fully human antibodies of any specificity and for diverse purposes. Recombinant antibodies can be engineered with optimized properties, such as antigen-binding affinity, molecular architecture and dimerization state, and fused with a vast array of effector moieties to enhance their tumor-targeting ability and potency. The use of gene therapy methods offers additional benefits by achieving sustained and effective concentrations of therapeutic antibodies directly at points of target intervention. This compensates for the rapid blood clearance of antibody fragments and could make the antibody less immunogenic and better tolerated. Furthermore, genetic approaches provide antibody molecules with new functions in unexpected scenarios: expression of antibody domains in precise intracellular locations and grafting of new binding activities to engineered cells. The relevance of these and other emerging concepts for antibody-based cancer therapy is discussed.