Ex vivo detectable activation of Melan-A-specific T cells correlating with inflammatory skin reactions in melanoma patients vaccinated with peptides in IFA

Cancer Immun. 2004 May 19;4:4.


The purpose of this study was to test melanoma vaccines consisting of peptides and immunological adjuvants for optimal immunogenicity and to evaluate laboratory immune monitoring for in vivo relevance. Forty-nine HLA-A2 positive patients with Melan-A positive melanoma were repeatedly vaccinated with Melan-A peptide, with or without immune adjuvant AS02B (QS21 and MPL) or IFA. Peptide-specific CD8 T cells in PBLs were analyzed ex vivo using fluorescent HLA-A2/Melan-A multimers and IFN-gamma ELISPOT assays. The vaccines were well tolerated. In vivo expansion of Melan-A-specific CD8 T cells was observed in 13 patients (1/12 after vaccination with peptide in AS02B and 12/17 after vaccination with peptide in IFA). The T cells produced IFN-gamma and downregulated CD45RA and CD28. T-cell responses correlated with inflammatory skin reactions at vaccine injection sites (P < 0.001) and with DTH reaction to Melan-A peptide (P < 0.01). Twenty-six of 32 evaluable patients showed progressive disease, whereas 4 patients had stable disease. The two patients with the strongest Melan-A-specific T-cell responses experienced regression of metastases in skin, lymph nodes, and lung. We conclude that repeated vaccination with Melan-A peptide in IFA frequently leads to sustained responses of specific CD8 T cells that are detectable ex vivo and correlate with inflammatory skin reactions.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, Neoplasm
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / toxicity
  • Dermatitis / etiology
  • Disease Progression
  • Female
  • Freund's Adjuvant / therapeutic use
  • Humans
  • Lipids / therapeutic use
  • Lymphocyte Activation
  • MART-1 Antigen
  • Male
  • Melanoma / diagnosis
  • Melanoma / immunology*
  • Melanoma / therapy
  • Middle Aged
  • Monitoring, Immunologic
  • Neoplasm Proteins / immunology*
  • Peptides / immunology
  • Peptides / therapeutic use
  • Viral Matrix Proteins / immunology


  • Antigens, Neoplasm
  • Cancer Vaccines
  • Lipids
  • M-protein, influenza virus
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Peptides
  • Viral Matrix Proteins
  • incomplete Freund's adjuvant
  • Freund's Adjuvant