Glycoengineered Yeast as an Alternative Monoclonal Antibody Discovery and Production Platform

Biologic pharmaceuticals are gaining in both market share and clinical utility compared with small molecule therapeutics (Projan et al., 2004). Global biologic drug sales reached $93 billion in 2009 and the sales are expected to grow at least twice as fast as those of small molecules (McCamish and Woollett, 2011). The rapid market growth and the promise of successful rate of developing biologic drugs has drawn the attention of traditional small molecule pharma into the biotechnology business. Today, more than ever, large pharmaceutical companies are venturing into the biotechnology arena with the hope that novel therapeutic proteins will augment the traditional pharmaceutical business enough to fundamentally reshape the market landscape. The acquisition/merging of pipeline and research capacity of biotech companies by big pharma is a great example of this trend. Several companies are even projecting optimistically that, within the decade, therapeutic biologics will comprise a majority of their commercial portfolios (Zhou, 2007). Among highly successful biologic products, monoclonal antibodies (mAbs) are the largest and fastest growing segment. MAbs are established as a key therapeutic modality for a range of diseases most notably rheumatoid diseases and various cancers. Due to the high degree of selectivity of these agents, in particular for cancer targets, they can be designed to selectively target tumor cells and elicit a variety of responses. These agents can kill cells directly by carrying a toxic payload to the target or can orchestrate the destruction of cells by activating immune system components, blocking receptors or sequestering growth factors (Nicolaides et al., 2010).