Engineered Antibody Offers potential Upgrade to IVIG Therapy

Intravenous immunoglobulin (IVIG) therapy involves infusing patients with naturally occurring IgG antibodies to treat autoimmune conditions. With origins dating back to the 1950s, IVIG is currently FDA-approved for four diseases but widely prescribed off-label to treat more than 80 additional ones because it’s often the only medicine that has any impact on these conditions.

But IVIG has serious shortcomings. Treatment can require multi-hour, high-volume infusions several times per month, the cost is exorbitant, and because the antibodies are sourced from donated human plasma, there are frequent supply shortages.

Now scientists from Rockefeller University’s Leonard Wagner Laboratory of Molecular Genetics and Immunology have used their discovery of previously unknown mechanisms in an anti-inflammatory pathway to develop a powerful upgrade: an engineered antibody that delivers the effectiveness of IVIG at a fraction of the dose in mice, and can be synthesized without the need for human plasma. They published their results in Science.

“We discovered that by enhancing the binding of a certain pair of receptors we can significantly lower the dose yet have an equal effect,” says first author Andrew Jones, a research associate in the lab, which is led by Jeffrey Ravetch.

These advances build upon earlier research from the lab that have already led them to develop a molecule 10 times more potent than IVIG, which is currently in phase 2 clinical trials through the biotech company Nuvig that Ravetch co-founded. The current findings dramatically improve upon that molecule.

40 years of research

the findings build on 40 years of research in Ravetch’s lab on Fc receptors, a family of proteins found on the surface of nearly all immune cells to which antibodies bind to coordinate the immune system’s effector responses. The most common serum antibody is immunoglobulin G (IgG), which represents 75% of the infection-fighting force found in blood-and is the key component of IVIG.

The work on the anti-inflammatory properties of IVIG began about 25 years ago when Ravetch discovered that a small fraction of serum IgGs present in IVIG possessed a naturally occurring modification: a sugar modification called sialylation, which conferred its anti-inflammatory properties. subsequent studies in his lab identified two additional components that were required to trigger an anti-inflammatory response by IVIG: an inhibit