Abstract

This chapter assesses advances in the understanding and manipulation of antibody binding sites and variable regions. The antigen binding region of an antibody reduced to a 25-kDa minimum comprises of a noncovalent heterodimer of V H and V L domains. Two potential therapeutic applications of antibody-enzyme fusion proteins are discussed in this chapter, in the treatment of occlusive vascular thrombosis and cancer. In addition to equilibrium binding affinity, the kinetic rate constants for antigen association with an antibody binding site and their dissociation are of particular interest. They are important to current discussions about what would be the most effective properties for targeted delivery of the therapeutic agents and what may be the natural limitations of the immune system. In certain cases, current research is viewed in the context of the early discoveries about antibodies to emphasize the continuity of protein chemistry in the field of immunology. This perspective reveals important generalizations that transcend the limits of studies based solely on polyclonal, monoclonal, or engineered antibodies.

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