ABSTRACT
INTRODUCTION Over the past 30 years, tremendous progress in the fi eld of biotechnology has produced over a hundred protein-and peptide-based pharmaceutical products approved for a broad spectrum of diseases ( 1 ). Current industry trends for molecules entering clinical development refl ect the growing importance of biopharmaceuticals, and an increasing number of these therapeutic agents will likely be commercially available in the near future ( 2 ). The growth in biopharmaceuticals is being fueled by advances in recombinant DNA and cell culture technologies ( 3 – 6 ) that enable large-scale and cost-effective production of exceedingly complex proteins including those containing post-translational modifi cations ( 7 ) that are often critical for their biological activity. Among the various classes of biotechnology-derived molecules being considered for therapeutic applications, monoclonal antibodies (mAbs) are currently receiving a great deal of attention from the pharmaceutical industry ( 1 , 8 – 14 ). The attractiveness of mAbs is largely based on their exquisite specifi city coupled with their potential to stimulate effector functionmediated immune responses ( 15 ) making them ideal candidates for targeted therapy of a variety of unmet medical needs. To date, there are over 20 mAbs approved worldwide for the treatment of a variety of cancers, autoimmune, and infl ammatory disorders as well as for diagnostic purposes with hundreds more in various stages of clinical development ( 14 , 16 – 18 ). Advances in protein engineering and genetic engineering technologies have now made it possible not only to develop monoclonal antibody molecules with the requisite specifi city and enhanced effi cacy, but also to humanize their amino acid sequence to decrease immunogenic potential ( 19 – 22 ).
