Evaluation of peptide vaccine immunogenicity in draining lymph nodes and peripheral blood of melanoma patients

Int J Cancer. 2001 Jun 1;92(5):703-11. doi: 10.1002/1097-0215(20010601)92:5<703::aid-ijc1250>3.0.co;2-5.


Many peptide epitopes for cytotoxic T lymphocytes (CTLs) have been identified from melanocytic differentiation proteins. Vaccine trials with these peptides have been limited mostly to those associated with HLA-A2, and immune responses have been detected inconsistently. Cases of clinical regression have been observed after peptide vaccination in some trials, but melanoma regressions have not correlated well with T-cell responses measured in peripheral blood lymphocytes (PBLs). We vaccinated stage IV melanoma patients with a mixture of gp100 and tyrosinase peptides restricted by HLA-A1 (DAEKSDICTDEY), HLA-A2 (YLEPGPVTA and YMDGTMSQV) and HLA-A3 (ALLAVGATK) in an emulsion with GM-CSF and Montanide ISA-51 adjuvant. CTL responses were assessed in PBLs and in a lymph node draining a vaccine site (sentinel immunized node, SIN). We found CTL responses to vaccinating peptides in the SIN in 5/5 patients (100%). Equivalent assays detected peptide-reactive CTLs in PBLs of 2 of these 5 patients (40%). CTLs expanded from the SIN lysed melanoma cells naturally expressing tyrosinase or gp100. We demonstrated immunogenicity for peptides restricted by HLA-A1 and -A3 and for 1 HLA-A2 restricted peptide, YMDGTMSQV. Immune monitoring of clinical trials by evaluation of PBLs alone may under-estimate immunogenicity; evaluation of SIN provides a new and sensitive approach for defining responses to tumor vaccines and correlating these responses with clinical outcomes. This combination of an immunogenic vaccine strategy with a sensitive analysis of CTL responses demonstrates the potential for inducing and detecting anti-tumor immune responses in the majority of melanoma patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Antigens, Neoplasm
  • Cancer Vaccines / immunology*
  • HLA-A Antigens / immunology*
  • Humans
  • Lymph Nodes / immunology*
  • Melanoma / immunology
  • Melanoma / therapy*
  • Melanoma-Specific Antigens
  • Membrane Glycoproteins / immunology*
  • Middle Aged
  • Molecular Sequence Data
  • Monophenol Monooxygenase / immunology*
  • Neoplasm Proteins / immunology*
  • Peptide Fragments / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • gp100 Melanoma Antigen


  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA-A Antigens
  • Melanoma-Specific Antigens
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PMEL protein, human
  • Peptide Fragments
  • gp100 Melanoma Antigen
  • Monophenol Monooxygenase