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DRB1*11 allele expression and HER2 pre-existing immunity may predict benefit in breast cancer patients vaccinated with the HER2 modified AE37 peptide vaccine

  • Eleftheria A Anastasopoulou1,
  • Panagiotis Tzonis1,
  • Sotirios P Fortis1,
  • Louisa Mahaira1,
  • Christoforos Vaxevanis1,
  • Alexandros Ardavanis2,
  • Elizabeth A Mittendorf3,
  • George E Peoples4,
  • Constantin N Baxevanis1,
  • Michael Papamichail1 and
  • Sonia A Perez1
Journal for ImmunoTherapy of Cancer20153(Suppl 2):P427

https://doi.org/10.1186/2051-1426-3-S2-P427

Published: 4 November 2015

Keywords

Breast Cancer PatientProstate Cancer PatientPeptide VaccineAllele ExpressionVaccine Group

Background

Identification of immune biomarkers indicating potential clinical benefit from immunotherapies may contribute to the selection of the right patient for the right therapy. We have recently reported that HLA-DRB1*11 and HLA-A*24 alleles might serve as predictive factors for immunological and clinical responses to vaccination with AE37, the Ii-Key hybrid peptide of HER2776-790 (AE36) in prostate cancer patients. The purpose of this study was to investigate the predictive significance of DRB1*11 allele expression in relation to immunological and clinical response in breast cancer patients vaccinated with AE37 in a randomized Phase II clinical trial.

Methods

This trial (ClinicalTrials.gov Identifier: NCT00524277) enrolled node-positive or high risk node-negative patients with any degree of HER2 expression (IHC 1-3+ or FISH > 1.2), rendered disease-free following standard of care therapy. Patients were randomized to receive either AE37+GM-CSF (vaccine group) or GM-CSF alone (control group) in 6 monthly intradermal primary inoculations followed by 4 boosters administered every 6 months. The current analysis includes data from 55 patients enrolled and vaccinated with AE37 in Greece, where the frequency of HLA-DRB1*11 is high. HLA-typing and measurement of TGFβ levels in serum were performed using Luminex® technology. Immunologic responses were assessed in vivo using the delayed-type hypersensitivity (DTH) test and in vitro with IFN-γ ELISPOT assay.

Results

Of the 55 vaccinated pts, 31 were found to be DRB1*11+ (56%). At baseline prior to vaccination, 22% (12 out of 55) of the vaccinated patients demonstrated pre-existing immunity against AE36 by IFN-γ release (defined as above the 75th percentile of all enrolled patients). Among patients with pre-existing AE36 immunity, the majority, 67% (8 out of 12), were found to be DRB1*11+. Vaccine-induced DTH and IFNγ responses, were augmented in the vast majority of DRB1*11+ patients. No correlation was observed between the pre-existing levels of serum TGFβ and the expression of the DRB1*11 allele. With a median follow up of 71 months, Kaplan-Meir analyses demonstrated a 22% and 72% relative reduction in recurrence rate (RRR) in DRB1*11+ patients and those with pre-existent immunity, respectively. Overall survival analysis of DRB1*11+ patients showed a 50% relative reduction in death rate (RRD), and a 74% RRD in patients with pre-existent immunity.

Conclusions

Our data demonstrate both immunologic and clinical advantage of vaccination therapy with AE37 among patients expressing DRB1*11 and/or having pre-existing HER2 immunity, highlighting their potential roles as predictive biomarkers to select patients most likely to benefit from vaccination with AE37.

Trial Registration

ClinicalTrials.gov identifier NCT00524277.

Authors’ Affiliations

(1)
Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece
(2)
St Savas Cancer Hospital, 1st Medical Oncology Clinic, Athens, Greece
(3)
The University of Texas MD Anderson Cancer Center, Houston, USA
(4)
Cancer Vaccine Development Program, San Antonio, USA

Copyright

© Anastasopoulou et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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