T cell receptor peptide vaccination in rheumatoid arthritis: A placebo-controlled trial using a combination of V?3, V?14, and V?17 Peptides

Abstract

IR501 therapeutic vaccine therapy was safe and well tolerated, immunogenic, and demonstrated clinical improvement in RA patients. Additional clinical trials are planned to confirm and extend these observations.

Dendritic cells and the promise of antigen-specific therapy in rheumatoid arthritis

“…Although modest benefits have been reported, these are all open-labelled studies (reviewed in [61]). Based on some early work suggesting that Vβ3, Vβ14 and Vβ17 determinants were dominant in RA, a trial was undertaken of Vβ3, Vβ14 and Vβ17 peptides emulsified in incomplete Freund's adjuvant [62]. Vaccination with a limited number of peptides on a population basis assumes the presence of public TCR determinants.…”

“…Vaccination with a limited number of peptides on a population basis assumes the presence of public TCR determinants. Given that patients were not recruited on the basis of a defined HLA-DR allele (no HLA typing was reported), the clinical effects of the peptide vaccination were predictably small [62]. …”

Restricted T-cell receptor β-chain usage by T cells autoreactive to β2–glycoprotein I in patients with antiphospholipid syndrome

“…Furthermore, in patients with rheumatoid arthritis, vaccination of a combination of peptides corresponding to the CDR2 sequences of V␤3, V␤14, and V␤17, which are predominantly expressed in synovial fluid and tissue, 35 diminished disease activity without any side effects. 36 TCR vaccination stimulated regulatory T cells that down-regulate pathogenic T cells without necessarily deleting them. 37,38 In this regard, in MS patients, V␤5.2-specific T-helper 2 cells induced by the V␤5.2 peptide vaccination directly inhibited MBP-reactive T helper 1 cells through the release of IL-10.…”

Targeting the T cell receptor in rheumatoid arthritis

“…The latter approach may depend on whcthcr pathogenic T cells in RA express a limited set of TCR. The report by Moreland et al, which appears elsewhere in this issue of Arthritis & Rheumatism (6), presents the initial results of a novel therapeutic strategy, TCK peptide vaccination, that attempts to target the TCRs on specific T cell subsets in RA.…”

“…subfamilies, which include about SO functional gene segments (14). The peptides used in the study by Moreland et al (6) are derived from the CDR2 of V,3, V,14, and V,l7 ( Figure 1A). These V region families together comprise about 10-15% of all V, regions expressed by CD4+ T cells (15).…”