Background: Peptide therapy targets T cells directly with short peptid
es containing multiple T-cell receptor epitopes. Murine studies sugges
t T cell anergy as the mechanism of action; however, changes in T-cell
cytokine profiles may be more relevant in human beings. Objective: We
sought to study the effects of peptide therapy on ex rivet antigen sp
ecific T-cell responses. Methods: Antigen-specific T cell lines were g
enerated from subjects enrolled in a double-blind, placebo controlled,
two-dose study of the ALLERVAX CAT therapeutic, containing Fel d 1 pe
ptide (ImmuLogic Pharmaceutical Corp., Waltham, Mass.) (n = 7, 8, and
7, respectively, for groups receiving placebo, 75 mu g, or 750 mu g).
Each subject had three lines propagated before and after receiving pep
tide therapy; antigens used were cat hair extract, Fel d I peptides, a
nd tetanus toroid (negative control), Proliferative responses and cyto
kine generation from each line were assessed after two restimulations
with antigen and autologous antigen-presenting cells. Results: The Fel
d 1 peptide lines showed a dose-dependent decrease of IL-4 production
(p = 0.02 and 0.025, respectively, for the 750 mu g group vs both the
75 mu g and placebo groups), IL-4 production from the cat hair allerg
en extract lines and interferon-gamma production from both the Fel d 1
peptide lines and cat hair allergen extract lines showed no statistic
ally significant changes. The control tetanus toroid lines showed no c
hanges in cytokine production; there were no significant changes in pr
oliferation with any of the antigens in any of the treatment groups. I
n the clinical arm of the trial, only the 750 mu g dose of peptides pr
oduced a significant response. Conclusions: Peptide therapy indices a
significant, dose-dependent decrease in peptide-stimulated IL-4 produc
tion, consistent with either a shift in T-cell phenotype or peptide-sp
ecific T-cell tolerance.