Vaccination of stage III/IV melanoma patients with long NY-ESO-1 peptide and CpG-B elicits robust CD8+ and CD4+ T-cell responses with multiple specificities including a novel DR7-restricted epitope

P. Baumgaertner, C. Costa Nunes, A. Cachot, H. Maby-El Hajjami, L. Cagnon, M. Braun, L. Derré, J. P. Rivals, D. Rimoldi, S. Gnjatic, S. Abed Maillard, P. Marcos Mondéjar, M. P. Protti, E. Romano, O. Michielin, P. Romero, D. E. Speiser, C. Jandus

Research output: Contribution to journalArticlepeer-review

Abstract

Long synthetic peptides and CpG-containing oligodeoxynucleotides are promising components for cancer vaccines. 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-ESO-179–108 peptide and CpG-B (PF-3512676), emulsified in Montanide ISA-51. In 18/18 evaluable patients, vaccination induced antigen-specific CD8+ and CD4+ T-cell and antibody responses, starting early after initiation of immunotherapy and lasting at least one year. The T-cells responded antigen-specifically, with strong secretion of IFNγ and TNFα, irrespective of patients' HLAs. The most immunogenic regions of the vaccine peptide were NY-ESO-189–102 for CD8+ and NY-ESO-183–99 for CD4+ T-cells. We discovered a novel and highly immunogenic epitope (HLA-DR7/NY-ESO-187–99); 7/7 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 induced integrated, robust and functional CD8+ and CD4+ T-cell responses in melanoma patients, supporting the further development of this immunotherapeutic approach.

Original languageEnglish
JournalOncoImmunology
Volume5
Issue number10
DOIs
Publication statusPublished - Oct 2 2016

Keywords

  • CpG-B
  • HLA-DR7
  • long synthetic peptide
  • malignant melanoma
  • NY-ESO-1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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