title: A pilot study in prostate cancer patients treated with the AE37 Ii-key-HER-2/neu polypeptide vaccine suggests that HLA-A*24 and HLA-DRB1*11 alleles may be prognostic and predictive biomarkers for clinical benefit.
abstract: Recently, several types of immunotherapies have been shown to induce encouraging clinical results, though in a restricted number of patients. Consequently, there is a need to identify immune biomarkers to select patients who will benefit from such therapies. Such predictive biomarkers may be also used as surrogates for overall survival (OS). We have recently found correlations between immunologic parameters and clinical outcome in prostate cancer patients who had been vaccinated with a HER-2/neu hybrid polypeptide vaccine (AE37) and received one booster 6 months post-primary vaccinations. Herein, we aimed to expand these retrospective analyses by studying the predictive impact of HLA-A*24 and HLA-DRB1*11 alleles, which are expressed at high frequencies among responders in our vaccinated patients, for clinical and immunological responses to AE37 vaccination. Our data show an increased OS of patients expressing the HLA-DRB1*11 or HLA-A*24 alleles, or both. Vaccine-induced immunological responses, measured as interferon γ (IFN-γ) responses in vitro or delayed-type hypersensitivity reactions in vivo, were also higher in these patients and inversely correlated with suppressor elements. Preexisting (i.e., before vaccinations with AE37) levels of vaccine-specific IFN-γ immunity and plasma TGF-β, among the HLA-A*24 and/or HLA-DRB1*11 positive patients, were strong indicators for immunological responses to AE37 treatment. These data suggest that HLA-DRB1*11 and HLA-A*24 are likely to be predictive factors for immunological and clinical responses to vaccination with AE37, though prospective validation in larger cohorts is needed.
authors.affiliation: Cancer Immunology and Immunotherapy Center, "Saint Savas" Cancer Hospital, 171 Alexandras Avenue, 11522, Athens, Greece.
authors.forename: Eleftheria A
authors.initials: EA
authors.lastname: Anastasopoulou
authors.forename: Ioannis F
authors.initials: IF
authors.lastname: Voutsas
authors.forename: Theodora
authors.initials: T
authors.lastname: Keramitsoglou
authors.forename: Cécile
authors.initials: C
authors.lastname: Gouttefangeas
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.forename: Anastasios
authors.initials: A
authors.lastname: Thanos
authors.forename: Michael
authors.initials: M
authors.lastname: Papamichail
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Perez
authors.forename: Constantin N
authors.initials: CN
authors.lastname: Baxevanis
mesh_terms: D000483:Alleles; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D059871:HLA-A24 Antigen / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000097:blood
chemical_list: D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D059871:HLA-A24 Antigen; D059811:HLA-DRB1 Chains; D018719:Erb-b2 Receptor Tyrosine Kinases; D016212:Transforming Growth Factor beta; C530655:AE37 vaccine; C508422:HLA-DRB1*11 antigen; C508053:ERBB2 protein, human