Multiepitope CD8(+) T cell response to a NY-ESO-1 peptide vaccine results in imprecise tumor targeting

J Clin Invest. 2002 Dec;110(12):1813-22. doi: 10.1172/JCI16428.


The cancer-testis antigen NY-ESO-1 is one of the most promising candidates for generic vaccination of cancer patients. Here we analyzed the CD8(+) T cell response to a NY-ESO-1 peptide vaccine composed of the two previously defined peptides 157-165 and 157-167, administered with GM-CSF as a systemic adjuvant. The NY-ESO-1 peptide vaccine elicited a CD8(+) T cell response directed against multiple distinct epitopes in the 157-167 region, as revealed by using A2/peptide multimers incorporating overlapping A2 binding peptides in this region. However, only a minor fraction of the elicited CD8(+) T cells, namely those recognizing the peptide 157-165 with sufficiently high functional avidity, recognized the naturally processed target on NY-ESO-1(+) tumor cells. In contrast, the majority of peptide 157-165-specific CD8(+) T cells exhibited lower functional avidity and no tumor reactivity. In addition, vaccine-elicited CD8(+) T cells specific for other overlapping epitopes in the 157-167 region failed to significantly recognize NY-ESO-1-expressing tumor targets. Thus, because of the complexity of the CD8(+) T cell repertoire that can be elicited by vaccination with synthetic peptides, a precise definition of the targeted epitope, and hence, of the corresponding peptide to be used as immunogen, is required to ensure a precise tumor targeting.

Publication types

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

MeSH terms

  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / metabolism
  • Cells, Cultured
  • Epitopes / immunology
  • Epitopes / metabolism*
  • HLA-A2 Antigen / immunology
  • HLA-A2 Antigen / metabolism
  • Humans
  • Leiomyosarcoma / immunology
  • Leiomyosarcoma / therapy
  • Male
  • Membrane Proteins*
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Protein Binding
  • Proteins / immunology*
  • Sarcoma, Synovial / immunology
  • Sarcoma, Synovial / therapy
  • Vaccines, Subunit / immunology*
  • Vaccines, Subunit / therapeutic use


  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Cancer Vaccines
  • Epitopes
  • HLA-A2 Antigen
  • Membrane Proteins
  • Proteins
  • Vaccines, Subunit