Glycoprotein-Based Therapeutics

It is known that carbohydrates have an essential and central role in a range of biological phenomena. For glycoprotein-based therapeutics such as rMAbs, the oligosaccharides... 

The reasons why drotrecogin alfa is included as a carbohydrate-based therapeutic is not only because it is a glycoprotein but also because to be fully active the core protein C must be glycosylated by the addition of four Asn-linked oligosaccharides. Other post-translational modifications required for activity include the addition of nine y-carboxy-ghita-... 

According to a review by Walsh [10], of 165 biopharmaceuhcal products approved in the United States and Europe by 2006, only two are nucleic acid-based drugs, whereas nine of the 31 therapeutic proteins approved since 2003 are produced in E, coli, and 17 are produced by mammalian cell lines. In 2004 market distribution and manufacture of therapeutic proteins, non-glycosylated (non-antibody) proteins constitutes 40% of the total market, with 12% armual growth rate, and are produced in E. coli or the yeast Saccharomyces cerevisiae glycoproteins (primarily mAbs) constitute 60% of the total market, with 26% armual growth rate, and are produced by mammalian cell culture (mostly with cells from Chinese Hamster Ovary, or CHO). 

The primary clinical targets of immunotoxins are tumors, based on the principle that the MAb will target the toxin to the tumor cells and the highly toxic moiety will then kill the cancer cells. Examples of toxins are ricin, diphtheria toxin and abrin, which are all glycoproteins. Their toxicity is based on their ability to block protein synthesis at the ribosomal protein assembly site. They are normally extremely toxic and not suitable for therapeutic purposes because they induce liver and vascular toxicity, even at low dose levels. 

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