Activation of human melanoma reactive CD8+ T cells by vaccination with an immunogenic peptide analog derived from Melan-A/melanoma antigen recognized by T cells-1

Clin Cancer Res. 2003 Feb;9(2):669-77.


Purpose: As compared with natural tumor peptide sequences, carefully selected analog peptides may be more immunogenic and thus better suited for vaccination. However, T cells in vivo activated by such altered analog peptides may not necessarily be tumor specific because sequence and structure of peptide analogs differ from corresponding natural peptides.

Experimental design: Three melanoma patients were immunized with a Melan-A peptide analog that binds more strongly to HLA-A*0201 and is more immunogenic than the natural sequence. This peptide was injected together with a saponin-based adjuvant, followed by surgical removal of lymph node(s) draining the site of vaccination.

Results: Ex vivo analysis of vaccine site draining lymph nodes revealed antigen-specific CD8+ T cells, which had differentiated to memory cells. In vitro, these cells showed accelerated proliferation upon peptide stimulation. Nearly all (16 of 17) of Melan-A-specific CD8+ T-cell clones generated from these lymph nodes efficiently killed melanoma cells.

Conclusions: Patient immunization with the analog peptide leads to in vivo activation of T cells that were specific for the natural tumor antigen, demonstrating the usefulness of the analog peptide for melanoma immunotherapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / therapeutic use
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines*
  • Flow Cytometry
  • Lymph Nodes / immunology
  • Lymphocyte Activation*
  • MART-1 Antigen
  • Melanoma / immunology*
  • Melanoma / therapy
  • Neoplasm Proteins / immunology*
  • Neoplasm Proteins / therapeutic use
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology


  • Antigens, Neoplasm
  • Cancer Vaccines
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Peptide Fragments