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Vaccination with long NY-ESO-1 79-108 peptide and CpG-B leads to robust activation of CD4 and CD8 T cell responses in stage III/IV melanoma patients, and a new HLA-DR7 epitope

  • Petra Baumgartner1,
  • Carla Costa Nunes2,
  • Amélie Cachot2,
  • Hélène Maby-El Hajjami3,
  • Laurène Cagnon4,
  • Marion Braun5,
  • Laurent Derré6,
  • Jean-Paul Rivals7,
  • Donata Rimoldi2,
  • Emanuela Romano4,
  • Olivier Michielin8,
  • Pedro Romero3,
  • Camilla Jandus2 and
  • Daniel E Speiser3
Journal for ImmunoTherapy of Cancer20153(Suppl 2):P437

https://doi.org/10.1186/2051-1426-3-S2-P437

Published: 4 November 2015

Keywords

PeptideMelanomaCell ResponseSynthetic PeptideMelanoma Patient

Although promising, the combination of long synthetic peptides and CpG-B oligodeoxynucleotides has not yet been tested as cancer vaccine. In this Phase I trial, 19 patients received a mean of 8 (range 1-12) monthly vaccines s.c. composed of the long synthetic NY-ESO79-108 peptide and CpG-B (PF-3512676), emulsified in Montanide ISA-51. In 18/18 evaluable patients, vaccination induced responses of both CD8 and CD4 T cells, starting early after initiation of immunotherapy and lasting for many months. The T cells responded antigen-specifically, with strong secretion of IFNγ and TNFα, irrespective of patient's HLAs. The most immunogenic region of the vaccine peptide was the NY-ESO-183-97 sequence, inducing HLA-DR or -DP restricted CD4 T cell responses in all patients tested. We discovered a novel and highly immunogenic epitope (HLA-DR7/NY-ESO-187-99); 5/5 HLA-DR7+ patients generated strong CD4 T cell responses, as detected directly ex-vivo with fluorescent multimers. Thus, vaccination with the long synthetic NY-ESO-179-108 peptide combined with the strong immune adjuvant CpG-B, a TLR-9 agonist, induced integrated, robust and functional CD8 and CD4 T cell responses in melanoma patients, supporting the further development of this immunotherapeutic approach.

Authors’ Affiliations

(1)
Ludwig Center for Cancer Research at the University of Lausanne and Department of Oncology, University Hospital of Lausanne, Lausanne, Switzerland
(2)
Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland
(3)
Department of Oncology, Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland
(4)
Department of Oncology, University Hospital Center (CHUV), Lausanne, Switzerland
(5)
Miltenyi Biotech GmbH, Bergisch Galdbach, Germany
(6)
Urology Research Unit, Urology Department, University Hospital Center (CHUV), Lausanne, Switzerland
(7)
Department of Otolaryngology, Head and Neck Surgery, University Hospital Center (CHUV), Lausanne, Switzerland
(8)
Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

Copyright

© Baumgartner 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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