ADCC Enhancement

GlymaxX®: Elegant Glyco-Engineering to Boost the ADCC Activity of Antibodies

This technology is based on the heterologous, cytosolic expression of a bacterial enzyme that redirects the de-novo fucose synthesis pathway towards a sugar-nucleotide that cannot be metabolized by the cell. The enzyme mediates the secretion of antibodies with minimized fucose content. The resulting modification of the glycostructure of IgG1 antibodies enhances their binding to NK cells and thus the ADCC response in potency assays. Consequently, the potency of the modified antibodies, directed against tumor or infected cells, is substantially increased.

The GlymaxX® technology ...

  • ... yields antibodies with a minimized fucose content
  • ... increases FcγRIIIa binding
  • ... can be applied to new and preexisting producer cell clones
  • ... can be engineered in less than 10 weeks
  • ... is applicable to different species
  • … requires no culture additives
  • … may even enhance productivity 
  • … is free-of-royalties
Figure 1: Antibodies produced from GlymaxX®-engineered cells contain a reduced amount of core-fucose and show an increased ability to recruit NK-cells and mediate an efficient antibody dependent cellular cytotoxicity (ADCC) response.
Figure 2: Working principle of the GlymaxX® Technology. In the absence of fucose, cells are unable to synthesize GDP-fucose via the salvage pathway. The de novo pathway, the dominant source of activated GDP-L-Fucose, is efficiently blocked by enzymatic conversion of the intermediate GDP-4-keto-6-deoxymannose into GDP-D-Rhamnose, a dead end product that typically does not occur in vertebrate cells.

For detailed information: 

Production of non-fucosylated antibodies by co-expression of heterologous GDP-6-deoxy-D-lyxo-4-hexulose reductase. 

von Horsten HH, Ogorek C., Blanchard V., Demmler C., Giese C., Winkler K., Kaup M., Berger M., Jordan I., Sandig V. 
Glycobiology. 2010 Dec; 20 (12):1607-18. Epub 2010 Jul 15.
PMID: 20639190 [PubMed – indexed for MEDLINE]