title: Biologics beyond TNF-α inhibitors and the effect of targeting the homologues TL1A-DR3 pathway in chronic inflammatory disorders.
abstract: A number of anti-tumor necrosis factor alpha (TNF-α) biologics have been developed in recent years, such as adalimumab, etanercept, and infliximab for the treatment of chronic inflammatory disorders like rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis and several other novel drugs that target TNF-α signaling are still being developed. Indeed, blockade of this pathway seems so important amongst immune-targets that TNF-α targeted therapies will continue to have a significant role in the treatment of chronic inflammation. However, up to 40% of RA and IBD patients do not respond to anti-TNF-α treatment and one possible explanation may be the heterogeneity of chronic inflammatory diseases and a dominance of other significant TNF family members. Indeed, polymorphisms in the TNF family member, TL1A gene, is associated with the development of IBD and increased serum concentrations of TL1A has been demonstrated in patients with various chronic inflammatory disorders. Here, we describe the current knowledge of TL1As immunobiology and present results from human disease, animal models, and pre-clinical intervention studies that point toward development of anti-TL1A therapy as a highly promising strategy for treatment of chronic inflammatory disorders.
authors.affiliation: a Department of Immunology and Microbiology, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark and.|b Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Tougaard
authors.affiliation: a Department of Immunology and Microbiology, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark and.
authors.forename: Kristoffer Alexander
authors.initials: KA
authors.lastname: Zervides
authors.affiliation: b Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Skov
authors.affiliation: b Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Axel Kornerup
authors.initials: AK
authors.lastname: Hansen
authors.affiliation: a Department of Immunology and Microbiology, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark and.
authors.forename: Anders Elm
authors.initials: AE
authors.lastname: Pedersen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; C117018:TL1 cytokine; C506033:TNFRSF25 protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: Biologics; TL1A; TNF; drug development; inflammation