Lysis of MYCN-amplified neuroblastoma cells by MYCN peptide-specific cytotoxic T lymphocytes

Cancer Res. 2000 Apr 1;60(7):1908-13.


The effectiveness of cell-mediated immunotherapy for cancer can be limited by loss-of-antigen mutations that occur during tumor growth. In neuroblastoma, amplification of the MYCN oncogene correlates with rapid tumor progression and a poor prognosis overall. We propose that the MYCN protein, the high-level expression of which is required for maintenance of the malignant phenotype, would be an ideal target for vaccine therapy. The MYCN-derived S9K peptide (amino acids 7-15; STMPGMICK), which contains an HLA-A1 binding motif, was used to generate CTLs from the peripheral blood lymphocytes of an HLA-A1+ healthy donor and an HLA-A1+ patient with MYCN-amplified neuroblastoma These CTL lines specifically lysed HLA-matched, MYCN-amplified neuroblastoma tumor cells. They did not lyse either HLA-mismatched, MYCN-amplified, or matched/nonmatched, non-MYCN-amplified tumor cells. The CTL activity was inhibited by a monoclonal antibody to a class I HLA monomorphic determinant but not by one specific for HLA class II, consistent with a class I-restricted mechanism of cytotoxicity. Antibodies to CD8, but not those to CD4, also inhibited CTL activity, identifying CD8+ lymphocytes as the effector cell population. These results show that MYCN-derived peptides can serve as tumor-specific antigens and suggest a rational approach to cell-mediated immunotherapy for MYCN-amplified neuroblastoma.

Publication types

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

MeSH terms

  • Adult
  • Antibodies, Monoclonal / pharmacology
  • Brain Neoplasms / genetics
  • Brain Neoplasms / immunology*
  • Brain Neoplasms / pathology
  • Child
  • Cytotoxicity, Immunologic
  • Female
  • Gene Amplification*
  • Genes, myc*
  • HLA-A1 Antigen / immunology
  • Humans
  • Infant
  • Male
  • Neuroblastoma / genetics
  • Neuroblastoma / immunology*
  • Neuroblastoma / pathology
  • Peptide Fragments / toxicity*
  • Proto-Oncogene Proteins c-myc / chemistry*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • HLA-A1 Antigen
  • Peptide Fragments
  • Proto-Oncogene Proteins c-myc