Monoclonal antibodies from plants: A new speed record

Abstract

The medical use of mAbs has grown tremendously since the first mAb, Orthoclone, was approved in 1986 for treatment of transplant rejection. In addition to immunosuppressive therapy, mAbs have proven useful as treatments for rheumatoid arthritis, transplant rejection, inflammatory diseases, and a variety of cancers. The market for medical mAbs is estimated to exceed $20 billion, and >150 are in clinical development (1). Although this progress is seemingly a biotechnology success story, the costs associated with a therapeutic mAb regimen can exceed $20,000 per year, which seriously may limit their current and future clinical use (2). These high costs are attributable to a number of factors, including the inherent expense of purification and cGMP for recombinant biologics and, to a significant extent, the cost of producing the raw material containing the antibody. To date, all Food and Drug Administration (FDA)-approved mAbs are derived from mammalian cells. Because of a reliance on relatively expensive equipment, an economy of scale may not be met by mammalian cell-based fermentation technology. This realization has fueled the development of numerous transgenic technologies during the last two decades that, it was hoped, would significantly lower production costs. These transgenic systems have involved transgenic yeast, bacteria, insects, animals, and plants (3). Each method appears to offer some advantages in scalability and cost, but they have all proven to possess distinct shortcomings precluding their acceptance by the larger scientific community, the medical community, or the FDA. These shortcomings include immunogenic glycosylation, propensity for viral pathogen copropagation, developmental instability, complex genetics, environmental concerns, and, most significantly, prolonged development times. One or more of these deficiencies is associated with every transgenic system, including current mammalian cell-based techniques. In this issue of PNAS, Giritch et al. (4) report significant progress in remedying several of these drawbacks but, most importantly, describe a …