Chapter 10. Antibodies and Derivatives

Summary

Monoclonal antibodies and antibody derivatives are among the fastest growing class of molecules being developed for a range of human diseases. Sophisticated, high-efficiency screening technologies developed recently may expedite the identification of antibodies with high potency and enhanced pharmaceutical properties. The design of a highly successful therapeutic product, Enbrel—a recombinant fusion product of TNF-α-receptor and immunoglobulin Fc—has benefited from maturation in knowledge about molecular and pharmacokinetic properties as well as detailed understanding of intricate biologic interactions of sequence determinants within antibody structure in vivo. Monoclonal antibodies, regardless of how they are made and what antigens they recognize, exhibit similar disposition profiles and, therefore, produce predictable pharmacokinetic properties. The development of new antibodies and human antibody derivatives for therapeutic use is thus greatly simplified. Using techniques for identification of sequence determinants that control antigen recognition, these determinants can be introduced in recombinant systems for large-scale production. In theory, the number of therapeutic antibodies that can be developed into drugs is limited only by the ability to identify antigens that hold the key to the therapeutic target. Such antigens could come from a range of pharmacologically and pathologically important receptors, cytokines, interferons, and other effector molecules. In addition to discussion of fundamental principles, the monograph section details relevant information for each antibody therapy.