title: T cell receptor peptide vaccination in rheumatoid arthritis: a placebo-controlled trial using a combination of Vbeta3, Vbeta14, and Vbeta17 peptides.
abstract: OBJECTIVE
  Restricted T cell receptor (TCR) gene usage has been demonstrated in animal models of autoimmune disease and has resulted in the successful use of TCR peptide therapy in animal studies. This clinical trial was undertaken to determine the safety and efficacy of a combination of Vbeta3, Vbeta14, and Vbeta17 TCR peptides in Freund's incomplete adjuvant (IFA) in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  A double-blind, placebo-controlled, multicenter, phase II clinical trial was undertaken using IR501 therapeutic vaccine, which consists of a combination of 3 peptides derived from TCRs (Vbeta3, Vbeta14, and Vbeta17) in IFA. A total of 99 patients with active RA received either 90 microg (n = 31) or 300 microg (n = 35) of IR501 or IFA alone (n = 33) as a control. The study medication and placebo were administered as a single intramuscular injection (1 ml) at weeks 0, 4, 8, and 20.
  
  
  RESULTS
  Treatment with IR501 was safe and well tolerated. None of the patients discontinued the trial because of treatment-related adverse events. Efficacy was measured according to the American College of Rheumatology 20% improvement criteria. Using these criteria, patients in both IR501 dosage groups showed improvement in disease activity. In the most conservative analysis used to evaluate efficacy, an intent-to-treat analysis including all patients who enrolled, the 90-microg dosage group showed a statistically significant improvement compared with control patients at the 20-week time point after the third injection. Trends toward improvement were shown in both the 90-microg and the 300-microg dosage groups at week 24 after the fourth injection.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The University of Alabama at Birmingham, Spain Rehabilitation Center, 35294, USA.
authors.forename: L W
authors.initials: LW
authors.lastname: Moreland
authors.forename: E E
authors.initials: EE
authors.lastname: Morgan
authors.forename: T C
authors.initials: TC
authors.lastname: Adamson
authors.forename: Z
authors.initials: Z
authors.lastname: Fronek
authors.forename: L H
authors.initials: LH
authors.lastname: Calabrese
authors.forename: J M
authors.initials: JM
authors.lastname: Cash
authors.forename: J A
authors.initials: JA
authors.lastname: Markenson
authors.forename: A K
authors.initials: AK
authors.lastname: Matsumoto
authors.forename: J
authors.initials: J
authors.lastname: Bathon
authors.forename: E L
authors.initials: EL
authors.lastname: Matteson
authors.forename: K M
authors.initials: KM
authors.lastname: Uramoto
authors.forename: C M
authors.initials: CM
authors.lastname: Weyand
authors.forename: W J
authors.initials: WJ
authors.lastname: Koopman
authors.forename: L W
authors.initials: LW
authors.lastname: Heck
authors.forename: V
authors.initials: V
authors.lastname: Strand
authors.forename: J P
authors.initials: JP
authors.lastname: Diveley
authors.forename: D J
authors.initials: DJ
authors.lastname: Carlo
authors.forename: C J
authors.initials: CJ
authors.lastname: Nardo
authors.forename: S P
authors.initials: SP
authors.lastname: Richieri
authors.forename: S W
authors.initials: SW
authors.lastname: Brostoff
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D001324:Autoantigens / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D005620:Freund's Adjuvant; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010446:Peptide Fragments / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D014611:Vaccination
chemical_list: D018501:Antirheumatic Agents; D001324:Autoantigens; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D005620:Freund's Adjuvant