It is based on Roche Schlieren's pioneering demonstration that antibody glycosylation can be engineered in a fashion which dramatically and specifically increases antibody-dependent cellular cytotoxicity (ADCC).
This immune effector mechanism is crucial for the in vivo target-cell killing activity of antibodies.
How GlycoMAb works
GlycoMAb® works by genetically engineering the antibody-producing cells with a gene encoding an oligosaccharide-modifying enzyme. The modified cells produce new molecular variants of the antibody, bearing bisected non-fucosylated oligosaccharides. These special oligosaccharides are not made by the standard production cell lines.
Antibodies produced using GlycoMAb® are highly enriched in bisected non-fucosylated glycosylation variants. The modified antibodies bind with higher affinity to the human FcgRIIIa receptor on immune effector cells. Increased binding affinity for this receptor translates into more efficient killing of the antibody-targeted cells by the immune effectors, a mechanism called antibody-dependent cellular cytotoxicity, or ADCC.
GlycoMAb® has the potential to address major challenges in the antibody field:
- Expanding the therapeutic window of a given antibody and providing treatment for patients which do not respond to current treatment options
- Reducing product attrition and avoiding costly failures, especially in late-stage clinical trials
- Enabling life cycle management by producing second generation versions of innovator’s own product
- Generating economically more attractive products (i.e., lower use of manufacturing capacity, reduced investment costs for manufacturing, reduced doses and frequency of injection, higher patient benefit and convenience)
- Providing a unique competitive advantage for unconjugated antibodies in a highly competitive market
Antibody-Dependent Cellular Cytotoxicity
ADCC potency increases of over 100-fold can be typically achieved with GlycoMAb® with the lowest being about 10-fold and the highest 10,000-fold, depending on the antibody and target cell. In the standard ADCC potency assay, target cells, antibody and freshly isolated immune effector cells are incubated together. After a few hours, the fraction of antibody-dependent target cell killing is determined.
GlycoMAb® in the Clinic
In the production of the clinical grade material, application of GlycoMAb did not change antibody productivity or cell growth. Very stable glycoengineered cell lines were generated and the production process remained unchanged.
It is based on Roche Glycart AG's pioneering demonstration that antibody glycosylation can be engineered in a fashion which dramatically and specifically increases antibody-dependent cellular cytotoxicity (ADCC). This immune effector mechanism is crucial for the in vivo target-cell killing activity of antibodies.