IgGZERO® Turns a Toxic Antibody into a Novel Treatment for Sepsis

April 16, 2020 | Applications, References |

Genovis SmartEnzyme IgGZERO was used in this recent study by researches from the University of Pennsylvania and the Philadelphia Children’s Hospital.

 

Sepsis is a dysregulated immune response to an infection that leads to very high levels of inflammation resulting in tissue damage and potential for multiorgan failure. It therefore leads to a high rate of mortality and morbidity. Neutrophil extracellular traps are part of the innate immune systems defence against infections where neutrophils rupture and release DNA, histones and many antimicrobial proteins. This however comes at a cost as NETs are degraded by circulating DNase and toxic degradation products are formed.

 

In a recent study published in Blood, researchers from the University of Pennsylvania and the Philadelphia Childrens Hosptial used a monoclonal antibody that binds to NETs to stabilize the traps, therefore significantly reducing the collateral tissue damage induced by NET degradation products. However, the mAb also activated the complement system and platelets, therefore negating the positive effect of NET stabilization. Using IgGZERO, the authors were able to remove the Fc glycosylation from their mAb, thereby impairing its ability to elicit an immune response. The deglycosylated mAb was still able to stabilize NETs and its administration lead to a significantly improved outcome in a murine sepsis model.

 

Fc glycosylation is a major determinant for which effector functions a monoclonal antibody is able to elicit and therefore its mode of action. Genovis IgG-specific endoglycosidases (GlycINATOR and IgGZERO) provide an easy way to remove the Fc glycans from mAbs.

 

Gollomp et al, 2020. Fc-modified HIT-like monoclonal antibody as a novel treatment for sepsis. Blood, 135(10), 743–754. doi:10.1182/blood.2019002329