Clinical efficacy of a new CD28-targeting antagonist of T cell co-stimulation in a non-human primate model of collagen-induced arthritisVierboom, M. P. M., Breedveld, E., Kap, Y. S., Mary, C., Poirier, N., 't Hart, B. A. & Vanhove, B., Mar-2016, In : Clinical and Experimental Immunology. 183, 3, p. 405-418 14 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||14|
|Journal||Clinical and Experimental Immunology|
|Publication status||Published - Mar-2016|
- CD28, CIA, co-stimulation blockade, rhesus monkey, T cell, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, ACTIVE RHEUMATOID-ARTHRITIS, CLASS-I REGION, RHESUS-MONKEYS, RENAL-ALLOGRAFT, DOUBLE-BLIND, ANTIBODIES, CTLA4IG, COSTIMULATION, ACTIVATION