Immunization with analog peptide in combination with CpG and montanide expands tumor antigen-specific CD8+ T cells in melanoma patients

J Immunother. 2008 Oct;31(8):781-91. doi: 10.1097/CJI.0b013e318183af0b.


Analog peptides represent a promising tool to further optimize peptide-based vaccines in promoting the expansion of tumor antigen-specific cytotoxic T lymphocytes. Here, we report the results of a pilot trial designed to study the immunogenicity of the analog peptide NY-ESO-1 157-165V in combination with CpG 7909/PF3512676 and Montanide ISA 720 in patients with stage III/IV NY-ESO-1-expressing melanoma. Eight patients were immunized either with Montanide and CpG (arm 1, 3 patients); Montanide and peptide NY-ESO-1 157-165V (arm 2, 2 patients); or with Montanide, CpG, and peptide NY-ESO-1 157-165V (arm 3, 3 patients). Only the 3 patients immunized with Montanide, CpG, and peptide NY-ESO-1 157-165V in arm 3 developed a rapid increase of effector-memory NY-ESO-1-specific CD8+ T cells, detectable ex vivo. The majority of these cells exhibited an intermediate/late-stage differentiated phenotype (CD28-). Our study further demonstrated that our vaccine approach stimulated spontaneous tumor-reactive NY-ESO-1-specific CD8+ T cells in 2 patients with advanced disease, but failed to prime tumor-reactive NY-ESO-1-specific T cells in 1 patient with no spontaneously tumor-induced CD8+ T-cell responses to NY-ESO-1. Collectively, our data support the capability of the analog peptide NY-ESO-1 157-165V in combination with CpG and Montanide to promote the expansion of NY-ESO-1-specific CD8+ T cells in patients with advanced cancer. They also suggest that the presence of tumor-induced NY-ESO-1-specific T cells of well-defined clonotypes is critical for the expansion of tumor-reactive NY-ESO-1-specific CD8+ T cells after peptide-based vaccine strategies.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Female
  • Humans
  • Immunization
  • Male
  • Mannitol / analogs & derivatives
  • Mannitol / therapeutic use
  • Melanoma / immunology*
  • Melanoma / therapy
  • Middle Aged
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / therapeutic use*
  • Oleic Acids / therapeutic use
  • Oligodeoxyribonucleotides / therapeutic use
  • Peptide Fragments / immunology
  • Peptide Fragments / therapeutic use*
  • Pilot Projects
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / therapy
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism


  • Cancer Vaccines
  • Neoplasm Proteins
  • Oleic Acids
  • Oligodeoxyribonucleotides
  • Peptide Fragments
  • ProMune
  • peptide NY-ESO-1 157-165
  • mannide monooleate
  • Mannitol