Genetically Engineered Antibodies in Gene Transfer and Gene Therapy

Abstract

Our ability to produce and engineer human monoclonal antibodies provides a basis for the development of novel therapeutical strategies against a variety of diseases. These strategies not only include improved passive immunotherapy but also more sophisticated antibody-based gene therapies involving gene transfer approaches. Four of the major applications of antibody gene engineering in the field of gene therapy are reviewed here. These are (1) the redefinition of viral vector tropism of infection for better transduction of cells of therapeutical interest, (2) the grafting of new cell recognition activities to effector cells of the immune system to kill cancer and pathogen-infected cells, (3) the inhibition of cellular and viral functions through intracellular expression of antibody-derived molecules, and (4) the systemic delivery of therapeutic monoclonal antibodies by non-B cells in living organisms.

Overview summary

Monoclonal antibodies are potentially useful for the treatment of many diseases. In this context, our ability to construct human monoclonal antibodies has constituted a major advance toward the passive immunization of human beings. Moreover, gene engineering not only permits the cloning of immunoglobulin genes, but also allows modifications of various types. These include improvement of kinetic/thermodynamic properties of antibodies, grafting of additional biological activities, and development of new classes of molecules. This extends considerably the scope of clinical applications of antibodies. Research by numerous groups worldwide indicates that antibody engineering may also prove advantageous in the field of gene therapy. Antibodies and antibody-related molecules may be used either for directing gene transfer vectors toward cells of therapeutic interest or as molecules with intrinsinc therapeutic activity. This article reviews major breakthroughs in this Field.