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

Vierboom, 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.

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  • Clinical efficacy of a new CD28-targeting antagonist of T cell co-stimulation

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DOI

  • M. P. M. Vierboom
  • E. Breedveld
  • Y. S. Kap
  • C. Mary
  • N. Poirier
  • B. A. 't Hart
  • B. Vanhove

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.

Original languageEnglish
Pages (from-to)405-418
Number of pages14
JournalClinical and Experimental Immunology
Volume183
Issue number3
Publication statusPublished - Mar-2016

    Keywords

  • 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

ID: 41414659