title: Clinical efficacy of a new CD28-targeting antagonist of T cell co-stimulation in a non-human primate model of collagen-induced arthritis.
abstract: T cells have a central pathogenic role in the aetiopathogenesis of rheumatoid arthritis (RA), and are therefore a favoured target of immunotherapy aiming at physical or functional elimination. Here we report an efficacy test of FR104, a new co-stimulation inhibitor directly targeting CD28 on T cells, in a translationally relevant model, the rhesus monkey model of collagen-induced arthritis (CIA). As a relevant comparator we used abatacept [cytotoxic T lymphocyte antigen immunoglobulin (CTLA Ig)], an antagonist of CTLA-4 binding to CD80/86 clinically approved for treatment of RA. Treatment with either compound was started at the day of CIA induction. Although FR104 previously demonstrated a higher control of T cell responses in vitro than abatacept, both compounds were equally potent in the suppression of CIA symptoms and biomarkers, such as the production of C-reactive protein (CRP) and interleukin (IL)-6 and anti-collagen type II (CII) serum antibody (IgM/IgG). However, in contrast to abatacept, FR104 showed effective suppression of CII-induced peripheral blood mononuclear cell (PBMC) proliferation. The current study demonstrates a strong potential of the new selective CD28 antagonist FR104 for treatment of RA.
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
authors.forename: M P M
authors.initials: MP
authors.lastname: Vierboom
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Breedveld
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
authors.forename: Y S
authors.initials: YS
authors.lastname: Kap
authors.affiliation: Institut National De La Santé Et De La Recherche Médicale, Université De Nantes, Effimune SA, Nantes, France.
authors.forename: C
authors.initials: C
authors.lastname: Mary
authors.affiliation: Institut National De La Santé Et De La Recherche Médicale, Université De Nantes, Effimune SA, Nantes, France.
authors.forename: N
authors.initials: N
authors.lastname: Poirier
authors.affiliation: Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.|Department Neuroscience, University of Groningen, University Medical Center, Groningen, the Netherlands.
authors.forename: B A
authors.initials: BA
authors.lastname: 't Hart
authors.affiliation: Institut National De La Santé Et De La Recherche Médicale, Université De Nantes, Effimune SA, Nantes, France.
authors.forename: B
authors.initials: B
authors.lastname: Vanhove
mesh_terms: D000069594:Abatacept / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000302:isolation & purification / Q000627:therapeutic use; D001169:Arthritis, Experimental; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D015551:Autoimmunity / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D018106:CD28 Antigens / Q000037:antagonists & inhibitors* / Q000276:immunology; D003094:Collagen / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects; D008253:Macaca mulatta; D008297:Male; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D018106:CD28 Antigens; D015850:Interleukin-6; D000069594:Abatacept; D003094:Collagen; D002097:C-Reactive Protein
keywords: CD28; CIA; T cell; co-stimulation blockade; rhesus monkey