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This fusion protein is composed of galectin-1 and galectin-3 and is a candidate therapeutic for modulating immune responses and treating inflammation. The global autoimmune disease therapeutics market should reach $1.5 billion by 2025. Galectins are promising therapeutic candidates for managing immune responses and inflammation because they can alter the phenotype and function of immune cells. Currently, galectin-1 and galectin-3 variants are used separately as therapeutics, but both require high doses that are expensive and impractical for clinical use.
Researchers at the University of Florida have developed a fusion protein composed of galectin-1 and galectin-3 that is a candidate therapeutic for regulating immune responses and controlling inflammation. This new candidate therapeutic displays greater binding ability, better immunomodulatory potency, and requires lower doses to be effective than other galectin therapeutics.
New galectin therapeutic with lower minimum effective dose and better binding in immune response regulation than other galectin therapeutics
This candidate therapeutic for regulating immune responses and controlling inflammation is a fusion protein comprised of one galectin-1 polypeptide and one galectin-3 polypeptide. This protein dimer has a better binding affinity and lower effective dosing requirement than current galectin candidate therapeutics, and it was more effective than other galectin therapeutics at inducing T-cell apoptosis critical for regulating immune responses.
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.
A stable, PEG-crosslinked Gal1 homodimer as an immunomodulatory therapeutic agent for chronic inflammatory and autoimmune diseases
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.
