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 scientiPage: 1 2 3 Related biology news :1
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