Potently Modulates the Immune Response in Autoimmune and Chronic Inflammatory Disease Conditions
This polymer crosslinked, more stable Galectin-1 homodimer suppresses inflammation more potently than unmodified recombinant Galectin-1. Galectin-1 (Gal1) modulates innate and adaptive immunity by regulating dendritic cell migration, inducing activated T cell apoptosis, and biasing Th1 and Th17 T-cell subsets toward immunosuppressive phenotypes. Prior work has shown that recombinant Gal1 suppresses T-cell-dependent chronic inflammation in diseases such as arthritis, hepatitis, and colitis. To retain its immune-modulating properties, Gal1 must adopt a homodimer conformation, which is an unstable structure. Using the synthetic polymer poly(ethylene glycol) (PEG) as a crosslinker provides a stable Gal1 homodimer. PEG is advantageous over other chemistries because it is well-tolerated by humans and has a proven track record as a therapeutic protein appendage.
Application
A stable, PEG-crosslinked Gal1 homodimer as an immunomodulatory therapeutic agent for chronic inflammatory and autoimmune diseases
Advantages
- Potential therapeutic treatment option for several inflammatory and autoimmune diseases such as arthritis, colitis, hepatitis, and allergic conjunctivitis
- Increases stability and potency, overcoming previously low availability of dimerized Gal1 concentrations for therapeutic purposes
- Easily manufactured and cost-effective, utilizing commercially available PEGDA and eliminating the use of a reducing agent in protein production
Technology
Translation of Galectin-1 (Gal1) therapies from bench to bedside has been unsuccessful. Gal1 administration is difficult because it typically requires high doses that favor the formation of the active homodimer conformation. This technology creates a more stable and potent therapeutic Gal1 by employing the synthetic polymer PEG as a crosslinker to stabilize homodimer formation. Although an abundance of pegylation exists in the protein-engineering field, the novelty of this system is using PEG with acrylates or maleimides at either end of polymer to attach onto two separate Gal1 monomers to create a stabilized dimeric structure.
Brochure
