Individualized synthetic peptide vaccines with GM-CSF in locally advanced melanoma patients

Cancer Biother Radiopharm. 2004 Dec;19(6):758-63. doi: 10.1089/cbr.2004.19.758.

Abstract

We report on 10 patients with resected American Joint Committee on Cancer (AJCC)stage IIA-IIIC melanoma receiving individualized adjuvant peptide vaccinations derived from the melanosomal antigens MelanA/MART1, gp100 and tyrosinase, according to patient tumor associated HLA restricted antigen expression, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF). Except for 1 patient, all patients had received systemic pretreatment with immunotherapy (n = 8), chemoimmunotherapy (n = 1), chemotherapy (n = 1), or cefalectin therapy (n = 1). Upon prior therapy, 7 of 10 patients had progressed with subcutaneous/cutaneous (n = 2), lymph node (n = 3), or subcutaneous/cutaneous and lymph node (n = 2)metastases, which were subsequently resected prior to vaccination. After a mean of 6.5 vaccination cycles, progression-free survival was 6 months (median, range 2-10). Five patients were relapse-free for 1+ up to 21+ months, 3 patients developed a solitary cutaneous metastasis, and 2 patients developed multiple metastases during vaccination. Overall, vaccine treatment was well tolerated, with no severe side-effects. Eight of 10 patients developed local delayed type hypersensitivity (DTH)reactions to synthetic peptides after the first or second injection. In 2 patients, transient fever, nausea, diarrhea, and muscle pain of National Cancer Institute (NCI)Grade I occurred. In summary, individualized synthetic peptide vaccination, combined with GM-CSF, was feasible and warrants further clinical investigation.

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm
  • Cancer Vaccines / therapeutic use*
  • Disease-Free Survival
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • HLA Antigens / metabolism
  • Humans
  • Lymph Nodes
  • Lymphatic Metastasis
  • MART-1 Antigen
  • Male
  • Melanoma / immunology
  • Melanoma / pathology
  • Melanoma / therapy*
  • Membrane Glycoproteins / immunology
  • Middle Aged
  • Monophenol Monooxygenase / immunology
  • Neoplasm Proteins / immunology
  • Neoplasm Staging
  • Peptide Fragments / immunology*
  • Peptide Fragments / therapeutic use
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Vaccination
  • gp100 Melanoma Antigen

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA Antigens
  • MART-1 Antigen
  • MLANA protein, human
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PMEL protein, human
  • Peptide Fragments
  • gp100 Melanoma Antigen
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Monophenol Monooxygenase