The technology will be used to aid in the manufacturing of selected ADCC (Antibody-Dependent Cell-Mediated Cytotoxicity) activity-enhanced antibodies in clinical and pre-clinical development at Novartis.
Volker Sandig, chief scientific officer at the German CDMO (contract development and manufacturing organization) ProBioGen, told BioPharma-Reporter.com, “The GlymaxX technology is aiming at removing fucose from the glycan attached to the CH2 domain of an antibody. It is known for more than a decade that this structural chance mediates a stronger binding to the receptor CD16 residing on NK [natural killer] cells.
“These cells play a major role in ADCC attacking tumor cells and or virus infected cells that are recognized by the respective antibody,” Sandig added.
ADCC enhancement has the potential to increase the therapeutic effect and/or to greatly reduce antibody dosage requirements, the company added.
"We are very satisfied that in our continuous business relationship Novartis has tested GlymaxX and, as a consequence, decided to integrate our GlymaxX technology into its own CHO cell line platform," said Volker Sandig, Chief Scientific Officer of German CDMO ProBioGen. “We are convinced that our GlymaxX technology will help to accelerate the drug development for any disease in which enhanced ADCC activity translates into therapeutic benefit.”
How the Tech Works
The GlymaxX technology for production of afucosylated proteins is based on the stable integration of a heterologous enzyme into any antibody producer cell line, leading to the interference with the cells’ intracellular fucose biosynthesis pathway.
“The technology provides a simple and robust alternative to other approaches for fucose reduction,” Sandig told us. “The gene for a specific Pseudomonas enzyme is introduced into the CHO producer cells; it utilizes an intermediate of the fucose synthetic pathway and converts it into Rhamnose that is foreign to mammalian cells.”
“Only a few molecules of the enzyme are sufficient to achieve almost complete afucosylation,” Sandig said. “Therefore, the effect is independent of expression levels, it is highly stable and well tolerated by the producer cell.”
The gene can also be introduced into existing producer cells or into starter cells of the platform, he added. The technology will be integrated into Novartis’ CHO platform.
Under the terms of the license agreement, ProBioGen grants Novartis non-exclusive rights to use the GlymaxX technology for an undisclosed number of clinical and pre-clinical development programs. Financial details were not disclosed.