Galectin-9 controls the therapeutic activity of 4-1BB-targeting antibodies
SCIE
SCOPUS
- Title
- Galectin-9 controls the therapeutic activity of 4-1BB-targeting antibodies
- Authors
- Madireddi, S; Eun, SY; Lee, SW; Nemcovicova, I; Mehta, AK; Zajonc, DM; Nishi, N; Niki, T; Hirashima, M; Croft, M
- Date Issued
- 2014-06-30
- Publisher
- Rockefeller University
- Abstract
- Biologics to TNF family receptors are prime candidates for therapy of immune disease. Whereas recent studies have highlighted a requirement for Fc gamma receptors in enabling the activity of CD40, TRAILR, and GITR when engaged by antibodies, other TNFR molecules may be controlled by additional mechanisms. Antibodies to 4-1BB (CD137) are currently in clinical trials and can both augment immunity in cancer and promote regulatory T cells that inhibit autoimmune disease. We found that the action of agonist anti-4-1BB in suppressing autoimmune and allergic inflammation was completely dependent on Galectin-9 (Gal-9). Gal-9 directly bound to 4-1BB, in a site distinct from the binding site of antibodies and the natural ligand of 4-1BB, and Gal-9 facilitated 4-1BB aggregation, signaling, and functional activity in T cells, dendritic cells, and natural killer cells. Conservation of the Gal-9 interaction in humans has important implications for effective clinical targeting of 4-1BB and possibly other TNFR superfamily molecules.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/10856
- DOI
- 10.1084/JEM.20132687
- ISSN
- 0022-1007
- Article Type
- Article
- Citation
- JOURNAL OF EXPERIMENTAL MEDICINE, vol. 211, no. 7, page. 1433 - 1448, 2014-06-30
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