Modulation of TNF receptor family members to inhibit autoimmune disease.
Certain members of the TNF-receptor family have shown proinflammatory function during immune activation and can be directly involved with the pathogenic effects observed during an autoimmune episode. The TNF-R family members summarized in this review includes: TNF-RI + II, OX40, and 4-1BB and they are expressed on a variety of leukocytes within the body. Studies within the last decade suggest that all of these proteins or their natural ligands can be targeted with various agents designed to diminish clinical signs of disease in autoimmune models. The data from the preclinical models specifically involving TNF-blockade have led to the development of clinical trials for patients with multiple sclerosis and rheumatoid arthritis. This review will chronicle the preclinical development of agents designed to inhibit OX40 and 4-1BB functions in autoimmunity and discuss relevant preclinical and clinical data associated with TNF-blockade.
Weinberg
Andrew D
AD
Department of Basic Immunology at the Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, OR 97213, USA. Andrew.Weinberg@providence.org
Montler
Ryan
R
D053330:4-1BB Ligand; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology; D053278:OX40 Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects* / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology
D053330:4-1BB Ligand; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D018124:Receptors, Tumor Necrosis Factor; C089251:TNFSF4 protein, human; C505974:TNFSF9 protein, human; D014409:Tumor Necrosis Factor-alpha