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:1/25/2016)... , Jan. 25, 2016  Glencoe Software, the world-leading ... and publication industries, will provide the data management solution ... (NPSC). ... Phenotypic analysis measures the ... organisms, allowing comparisons between states such as health and ...
(Date:1/21/2016)... , January 21, 2016 ... to a new market research report "Emotion Detection and ... Others), Software Tools (Facial Expression, Voice Recognition and ... - Global forecast to 2020", published by MarketsandMarkets, ... expected to reach USD 22.65 Billion by 2020, ...
(Date:1/20/2016)... JOSE, Calif. , Jan. 20, 2016 /PRNewswire/ ... developer of human interface solutions, today announced sampling ... controller solution for wearables and small screen applications ... such as printers. Supporting round and rectangular shapes, ... S1423 offers excellent performance with moisture on screen, ...
Breaking Biology News(10 mins):
(Date:2/10/2016)...  Allergan plc (NYSE: AGN ) a leading ... , Allergan,s CEO and President, will be featured as ... the RBC Capital Markets Healthcare Conference on Tuesday, February ... York Palace Hotel in New York, NY ... can be accessed on Allergan,s Investor Relations web site ...
(Date:2/10/2016)... ... February 10, 2016 , ... SonaCare Medical, LLC reports ... program, Sonalink™ remote monitoring. The inaugural launch of this new technology occurred over ... Dr. Samuel Peretsman to a HIFU technical expert at SonaCare Medical headquarters. ...
(Date:2/10/2016)... ... February 09, 2016 , ... Creation Technologies, ... of the Highest Overall Customer Rating Award from Circuits Assembly , today announced ... across the USA, Canada, Mexico and China. , The EMS provider, known in ...
(Date:2/9/2016)... ... 2016 , ... Clinovo , the cloud-based eClinical software ... Capture (EDC) system ClinCaptureand its new Contract Research Organization (CRO) Partner Program ... San Mateo, California on February 10th and 11th. Watch 2-min video . ...
Breaking Biology Technology: