Peptide vaccination of patients with metastatic melanoma: improved clinical outcome in patients demonstrating effective immunization

Am J Clin Oncol. 2006 Aug;29(4):352-60. doi: 10.1097/01.coc.0000217877.78473.a4.


Objectives: Therapeutic peptide vaccines for melanoma continue to only demonstrate anecdotal success. We set out to evaluate the impact of low-dose GM-CSF emulsified in Montanide ISA-51 on the immunogenicity of HLA-A2 restricted melanoma differentiation antigen peptide vaccines (MART-1, gp100 and tyrosinase) administered in separate subcutaneous injections.

Methods: We conducted a randomized phase II clinical trial of HLA-A2+ patients with metastatic melanoma that were immunized every 3 weeks with one of the following vaccine preparations: (A) peptides + Montanide ISA-51; (B) peptides + Montanide ISA-51 + GM-CSF (10 microg); (C) peptides + Montanide ISA-51 + GM-CSF (50 microg). Immunization efficacy was determined by quantification of vaccine specific tetramer positive cytotoxic T cells in peripheral blood. Global assessment of immune competence was ascertained using DTH testing to common recall antigens as well as peripheral blood immunophenotyping.

Results: Twenty-five eligible patients were equally distributed across all 3 treatment groups. Only 9 patients demonstrated evidence of immunization. Most commonly, immune response was achieved to the gp100 peptide. The addition of low-dose GM-CSF did not impact immunization efficacy. DTH reactivity to Candida appeared predictive of successful immunization. Successful immunization with the peptide vaccines was associated with improved clinical outcomes.

Conclusions: The addition of low dose GM-CSF to peptide vaccines did not enhance immunogenicity. Higher doses of GM-CSF may be needed to achieve this effect and this is a testable hypothesis. Likewise, better patient selection based on immunologic status (DTH reactivity) may be helpful to better understand the clinical impact of therapeutic cancer vaccines.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • HLA-A2 Antigen / immunology
  • Humans
  • Hypersensitivity, Delayed
  • Immunophenotyping
  • MART-1 Antigen
  • Male
  • Mannitol / administration & dosage
  • Mannitol / analogs & derivatives
  • Melanoma / immunology
  • Melanoma / secondary
  • Melanoma / therapy*
  • Membrane Glycoproteins / immunology
  • Middle Aged
  • Monophenol Monooxygenase / immunology
  • Neoplasm Proteins / immunology*
  • Oleic Acids / administration & dosage
  • Recombinant Proteins
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Survival Analysis
  • Vaccines, Subunit / immunology
  • Vaccines, Subunit / therapeutic use*
  • gp100 Melanoma Antigen


  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA-A2 Antigen
  • MART-1 Antigen
  • MLANA protein, human
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Oleic Acids
  • PMEL protein, human
  • Recombinant Proteins
  • Vaccines, Subunit
  • gp100 Melanoma Antigen
  • montanide ISA 51
  • Mannitol
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Monophenol Monooxygenase