Navigation Links
GlycoFi announces the first production of antibodies with human glycosylation in yeast

Researchers at GlycoFi and Dartmouth College have reported the first production of monoclonal antibodies with human sugar structures in yeast.

This research, published online January 22 and in the February issue of the journal Nature Biotechnology, demonstrates that antibodies with human sugar structures (glycosylation) can be produced in glyco-engineered yeast cell lines, and that by controlling the sugar structures of antibodies, their therapeutic potency can be significantly improved. Moreover, this same approach offers the potential to improve other glycosylation-dependent drug properties (such as solubility, half-life, or tissue distribution). Given the mature and well-established nature of yeast-based protein production technology, the reported work also promises to improve the production and scale-up economics of antibody manufacturing.

Monoclonal antibodies constitute the majority of therapeutic proteins currently in clinical and preclinical development, and additionally represent some of the largest selling products to emerge from the biotechnology industry. Monoclonal antibodies often achieve their therapeutic benefit through two binding events: 1) the binding of the variable domain of the antibody to a specific marker protein, such as the CD20 receptor on the surface of cancer cells, followed by 2) the recruitment of immune system "effector" cells that bind the constant domain of the antibody and destroy the cancer cell to which the antibody is bound. Research has shown that this process, known as antibody dependent cell cytotoxicity (ADCC), is sensitive to the composition of sugars (or "glycans") in the antibody's constant region. Moreover, in the absence of these sugars, the antibodies can bind to antigens but do not elicit ADCC.

"Mammalian cell cultures currently used for most therapeutic protein production produce a mixture of glycoforms and typically do not allow for the control of glycosylation," said Tillman Gerngross, chief scientific officer of GlycoFi, and professor of Bioengineering at Dartmouth College. "We have spent the last five years engineering yeast cell lines that perform human glycosylation, which now allows us to glycosylate proteins with unprecedented control and uniformity."

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 tain a large array of specific glycoprotein variants that were hitherto unobtainable at a commercial scale. The company believes that as the scale-up and recombinant production of proteins in yeast is a well established technology, more easily achieved than mammalian cell culture, it should be possible to produce specific designer glycoproteins at large scale using the company's engineered yeasts. GlycoFi has already announced several major collaborations aimed at applying its technology to the production of specific therapeutic proteins, including collaborations with Merck, Eli Lilly and others.


'"/>

Source:JKureczka@comcast.net


Related biology news :

1. GlycoFi and Dartmouth report full humanization of yeast glycosylation pathway in Science
2. Wiley announces publication of Databasing the Brain
3. Nonlinear Dynamics announces more details of its global partnership with PerkinElmer
4. Neurologix announces positive results of gene therapy clinical trial in Parkinsons disease
5. Eisai announces Phase II data on E7389, a potential new therapy for the treatment of breast cancer
6. NHGRI announces new sequencing targets
7. CHAVI announces international search for genes affecting HIV response
8. NHGRI announces latest sequencing targets
9. MUHC announces a transplant first in Quebec
10. St. Jude announces breakthrough in eye cancer treatment
11. NIH announces phase III clinical trial of creatine for Parkinsons disease
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/10/2017)... 2017 Research and Markets has ... Medicine - Scientific and Commercial Aspects" to their offering. ... ... integrated with therapy for selection of treatment as well for ... prevention of disease in modern medicine. Biochip/microarray technologies and next ...
(Date:2/8/2017)... , Feb. 7, 2017 Report Highlights ... The global synthetic-biology ... $11.4 billion by 2021, growing at a compound annual growth ... An overview of the global markets for synthetic biology. - ... for 2016, and projections of compound annual growth rates (CAGRs) ...
(Date:2/7/2017)... 2017 Zimmer Biomet Holdings, Inc. (NYSE and ... present at the LEERINK Partners 6th Annual Global Healthcare ... Wednesday, February 15, 2017 at 10 a.m. Eastern Time. ... can be accessed at http://wsw.com/webcast/leerink28/zbh .  The webcast ... Zimmer Biomet,s Investor Relations website at http://investor.zimmerbiomet.com . ...
Breaking Biology News(10 mins):
(Date:2/23/2017)... ... February 23, 2017 , ... ... a published evaluation of multiple immunoassay-based threat detection technologies by researchers from ... PathSensors’ CANARY® biosensor threat detection technology was found to have the best ...
(Date:2/23/2017)... , ... February 23, 2017 , ... The Greater ... a new partnership with Compass Research . GGI's mission is to advance global ... to a child in need in honor of each clinical trial volunteer. The vision ...
(Date:2/23/2017)... DIEGO and SAN FRANCISCO ... a privately-held regenerative medicine company, and Beyond Type 1, ... with type 1 diabetes, today announced a grant from ... a functional cure for type 1 and other insulin-requiring ... ViaCyte has been developing innovative stem cell-derived cell replacement ...
(Date:2/22/2017)... ... February 22, 2017 , ... Kernel , ... Research Systems, LLC (KRS) clinical development program. KRS is a neurotechnology spin-out ... research and clinical applications. The terms of the transaction were not disclosed. ...
Breaking Biology Technology: