Humanized antibodies currently are produced through mammalian cell culture methods that require extensive resources, in particular, choosing the manufacturing cell line and the need for highly specialized cell growth facilities. These limitations have highlighted the need for new and more innovative ways for antibody production. Yeast heterologous protein expression systems have long been viewed as efficient and high yielding alternatives for mammalian cell line production. Yeast is able to deal with important folding and export issues that are unique to proteins found in higher eukaryotes, makes use of inexpensive media, has much greater routine commercialization, and enables significant reduction in cost and time for production. Antibody expression in this host provides an excellent solution for more efficient and expanded application of this class of therapeutics. In the case of antibodies, correct glycosylation was viewed a required feature. However, recent studies have questioned this requirement. Aglycosylated antibodies have been described to have comparable half-lives and retain function when the post-translational modification is eliminated. It is in this light that our proposal focuses on the use of Pichia pastoris as a new host for full-length antibody expression building on the extensive success this system has had for the production of therapeutic proteins
