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Asthma; multiple sclerosis (MS)

Galectin-9 (LGALS9); tumor necrosis factor receptor superfamily member 9 (TNFRSF9; 4-1BB; CD137)

Mouse and in vitro studies suggest LGALS9 is required for the efficacy of anti-4-1BB antibodies in inflammatory and autoimmune disease. In a mouse experimental autoimmune encephalomyelitis (EAE) model of MS and a mouse model of allergic asthma, anti-4-1BB antibodies caused near-complete suppression of disease development in wild-type mice but failed to protect Lgals9-deficient mice. In vitro assays showed that human LGALS9 bound to 4-1BB at a carbohydrate-recognition domain and that binding is prevented when the site is deglycosylated. Researchers did not disclose next steps, which could include identifying LGALS9 agonists.
Pfizer Inc. has the anti-TNFRSF9 mAb PF-05082566 in Phase I testing to treat cancer and non-Hodgkin's lymphoma.
Bristol-Myers Squibb Co. has the TNFRSF9-targeting mAb urelumab (BMS-663513) in Phase I testing to treat solid tumors.

SciBX 7(29); doi:10.1038/scibx.2014.874
Published online July 31, 2014

Patent application filed; available for licensing

Madireddi, S. et al. J. Exp. Med.; published online June 23, 2014;
Contact: Michael Croft, La Jolla Institute for Allergy & Immunology,
La Jolla, Calif.