In the study described in Nature Biotechnology, the researchers used several glyco-engineered yeast cell lines to produce a library of glycoforms of the anti-CD20 antibody rituximab and to compare their receptor binding properties to the mammalian-derived commercial counterpart, Rituxan®. The polypeptide backbone of each of the antibody variants produced in the GlycoFi yeast remained identical and only the glycosylation structures of each antibody was altered. Comparisons of the antibody variants with Rituxan® showed that antibody binding varied with changes in the glycosylation structure. Moreover certain antibody glycoforms showed significantly increased antibody mediated cell killing compared to Rituxan®.
"By controlling the sugar structures on antibodies we have shown that the antibodies ability to kill cancer cells can be significantly improved and that therapeutic proteins can be optimized by controlling their sugar structures," says Dr. Huijuan Li, associate director of Analytical Development at GlycoFi, and the lead author of the study. She noted that while the current report focuses on antibodies, the approach taken by the GlycoFi team can be applied to any therapeutic glycoprotein. Moreover, in addition to cell killing, this approach can be applied to optimize other protein characteristics such as solubility, therapeutic half-life, tissue distribution and interaction with complement proteins. Currently glycoproteins comprise about 70% of all approved therapeutic proteins and the therapeutic protein market is expected to grow at over 20% annually over the next decade.
GlycoFi is now working to expand its library of glyco-engineered yeast cell lines and expects to ob