Overview on the Use of Therapeutic Antibodies in Drug Discovery

Abstract

The number of therapeutic antibodies approved by regulatory agencies as novel drugs and the number of antibodies in development has increased significantly. The modular nature of antibody structure has enabled researchers to more predictably design therapeutic antibodies by choosing appropriate functional features most appropriate for a given antibody target and clinical indication. Advances in recombinant antibody technologies have allowed the routine generation of antibodies that can satisfy stringent drug design criteria, such as low immunogenicity, high affinity, target specificity, and commercially viable manufacturing methods. Engineering design opportunities exist for both the variable and the constant regions that encompass, in addition to antigen specificity and affinity, effector functions that mediate immune complex clearance or pharmacokinetics. These are discussed in the context of relevant in vivo and in vitro technologies, such as human IgG transgenic mice, phage display, and biologics manufacturing. Finally, therapeutic antibodies are compared with traditional drugs with respect to target class, selectivity, route of administration, intellectual property issues, and lead discovery and optimization.

Therapeutic Monoclonal Antibodies against Cancer: Present and Future

“…Other methodologies employ in vitro transcription-translation reactions, ribosome display, or mRNA display that correlate an antibody to its mRNA. These technologies and the appropriate protocols are described by Zoguska et al [151]. The advantage of these technologies is that antibody humanization is not required.…”

“…The advantage of these technologies is that antibody humanization is not required. However, the lead identification phase for the display technologies allows in general the selection of low-affinity antibodies and requires a lead optimization phase in which improved variants should be generated and selected [151].…”