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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.
AuthorsEleftheria A Anastasopoulou, Ioannis F Voutsas, Theodora Keramitsoglou, Cécile Gouttefangeas, Hubert Kalbacher, Anastasios Thanos, Michael Papamichail, Sonia A Perez, Constantin N Baxevanis
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 64 Issue 9 Pg. 1123-36 (Sep 2015) ISSN: 1432-0851 [Electronic] Germany
PMID26026288 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • AE37 vaccine
  • Biomarkers, Tumor
  • Cancer Vaccines
  • HLA-A24 Antigen
  • HLA-DRB1 Chains
  • HLA-DRB1*11 antigen
  • Transforming Growth Factor beta
  • ERBB2 protein, human
  • Receptor, ErbB-2
Topics
  • Alleles
  • Biomarkers, Tumor (genetics, immunology)
  • Cancer Vaccines (administration & dosage, immunology)
  • HLA-A24 Antigen (biosynthesis, genetics, immunology)
  • HLA-DRB1 Chains (biosynthesis, genetics, immunology)
  • Humans
  • Male
  • Pilot Projects
  • Prognosis
  • Prostatic Neoplasms (blood, genetics, immunology, therapy)
  • Receptor, ErbB-2 (biosynthesis, immunology)
  • Transforming Growth Factor beta (blood)

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