Clinical efficacy of a new CD28‐targeting antagonist of T cell co‐stimulation in a non‐human primate model of collagen‐induced arthritis

• Published in: Clinical and experimental immunology 2016-03, Vol.183 (3), p.405-418
• Main Authors: Vierboom, M. P. M., Breedveld, E., Kap, Y. S., Mary, C., Poirier, N., 't Hart, B. A., Vanhove, B.
• Format: Article
• Language: English
• Subjects: Abatacept - administration & dosage; Abatacept - therapeutic use; Animals; Antirheumatic Agents - administration & dosage; Antirheumatic Agents - isolation & purification; Antirheumatic Agents - therapeutic use; Arthritis; Arthritis, Experimental; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Autoimmunity - drug effects; C-Reactive Protein - metabolism; CD28; CD28 Antigens - antagonists & inhibitors; CD28 Antigens - immunology; CIA; Collagen; Collagen - immunology; co‐stimulation blockade; Drug Administration Schedule; Female; Humans; Interleukin-6 - blood; Lymphocyte Activation - drug effects; Macaca mulatta; Male; Original; rhesus monkey; T cell; T cell receptors; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - physiology; Translational; Treatment Outcome
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.12739

Summary 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.