Major histocompatibility complex-restricted lysis of neuroblastoma cells by autologous cytotoxic T lymphocytes

J Immunother. 2001 Jul-Aug;24(4):305-11. doi: 10.1097/00002371-200107000-00006.


Vigorous host immune reactivity to neuroblastoma may correlate with better prognosis, but identification of human cytotoxic T-lymphocyte (CTL) responses has been relatively unsuccessful. We generated neuroblastoma-reactive CTL lines from two human leukocyte antigen (HLA) A2+ neuroblastoma patients by stimulation of peripheral blood lymphocytes (PBLs) with irradiated autologous tumor cells pretreated with interferon-gamma in the presence of low concentrations of interleukin-2 (5 U/mL). These lines lyse autologous tumor cells but do not kill HLA mismatched allogeneic tumor cells, Epstein-Barr virus-transformed autologous B cells, or standard natural killer cell targets. Cytotoxic T lymphocytes generated from one patient recognize tumor cells from several HLA-A2 matched children, although the other patient's CTLs do not kill tumor cells from other HLA-A2+ individuals. Pretreatment of CTLs or target cells with appropriate standard monoclonal antibodies demonstrates that these CTLs are major histocompatibility complex class I (HLA-A2) restricted and that the effector cell population is CD8+. Our findings suggest that these tumor cells express at least one common HLA-A2 restricted antigen and at least one unique private epitope. Autologous tumor-specific CTLs can be readily generated from patients' PBLs and maintained in long-term culture using standard techniques.

Publication types

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

MeSH terms

  • Antigens, Neoplasm / immunology
  • Cell Line
  • Child
  • Child, Preschool
  • Epitopes
  • Female
  • HLA-A2 Antigen / immunology*
  • Humans
  • Infant
  • Male
  • Neuroblastoma / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured


  • Antigens, Neoplasm
  • Epitopes
  • HLA-A2 Antigen