title: Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial.
abstract: OBJECTIVE
  To assess the safety, tolerability, and efficacy of spliceosomal peptide P140 (IPP-201101; sequence 131-151 of the U1-70K protein phosphorylated at Ser140), which is recognized by lupus CD4+ T cells, in the treatment of patients with systemic lupus erythematosus (SLE).
  
  
  METHODS
  An open-label, dose-escalation phase II study was conducted in two centers in Bulgaria. Twenty patients (2 male and 18 female) with moderately active SLE received 3 subcutaneous (SC) administrations of a clinical batch of P140 peptide at 2-week intervals. Clinical evaluation was performed using approved scales. A panel of autoantibodies, including antinuclear antibodies, antibodies to extractable nuclear antigens (U1 RNP, SmD1, Ro/SSA, La/SSB), and antibodies to double-stranded DNA (anti-dsDNA), chromatin, cardiolipin, and peptides of the U1-70K protein, was tested by enzyme-linked immunosorbent assay (ELISA). The plasma levels of C-reactive protein, total Ig, IgG, IgG subclasses, IgM, IgA, and IgE, and of the cytokines interleukin-2 and tumor necrosis factor alpha were measured by ELISA and nephelometry.
  
  
  RESULTS
  IgG anti-dsDNA antibody levels decreased by at least 20% in 7 of 10 patients who received 3 x 200 microg IPP-201101 (group 1), but only in 1 patient in the group receiving 3 x 1,000 microg IPP-201101 (group 2). Physician's global assessment of disease activity scores and scores on the SLE Disease Activity Index were significantly decreased in group 1. The changes occurred progressively in the population of responders, increased in magnitude during the treatment period, and were sustained. No clinical or biologic adverse effects were observed in the individuals, except for some local irritation at the highest concentration.
  
  
  CONCLUSIONS
  IPP-201101 was found to be safe and well tolerated by subjects. Three SC doses of IPP-201101 at 200 microg significantly improved the clinical and biologic status of lupus patients.
authors.affiliation: CNRS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France. S.Muller@ibmc.u-strasbg.fr
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
authors.forename: Fanny
authors.initials: F
authors.lastname: Monneaux
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schall
authors.forename: Rasho K
authors.initials: RK
authors.lastname: Rashkov
authors.forename: Boycho A
authors.initials: BA
authors.lastname: Oparanov
authors.forename: Philippe
authors.initials: P
authors.lastname: Wiesel
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Geiger
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D004247:DNA / Q000276:immunology; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000138:chemical synthesis; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000138:chemical synthesis; D012720:Severity of Illness Index; D017381:Spliceosomes; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D010446:Peptide Fragments; D010455:Peptides; C535176:spliceosomal peptide P140; D002097:C-Reactive Protein; D004247:DNA