Spliceosomal peptide P140 for immunotherapy of systemic lupus erythematosus: results of an early phase II clinical trial.
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.
Muller
Sylviane
S
CNRS, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France. S.Muller@ibmc.u-strasbg.fr
Monneaux
Fanny
F
Schall
Nicolas
N
Rashkov
Rasho K
RK
Oparanov
Boycho A
BA
Wiesel
Philippe
P
Geiger
Jean-Marie
JM
Zimmer
Robert
R
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
D000974:Antibodies, Antinuclear; D010446:Peptide Fragments; D010455:Peptides; C535176:spliceosomal peptide P140; D002097:C-Reactive Protein; D004247:DNA