Identification of EGFRvIII-derived CTL epitopes estricted by HLA A0201 for dendritic cell based immunotherapy of gliomas

An Hua Wu, Jing Xiao, Lars Anker, Walter A. Hall, Dale S. Gregerson, Webster K. Cavenee, Wei Chen, Walter C. Low

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The type III variant of the epidermal growth factor receptor (EGFRvIII) mutation is present in 20-25% of patients with glioblastoma multiforme (GBM). EGFRvIII is not expressed in normal tissue and is therefore a suitable candidate antigen for dendritic cell (DC) based immunotherapy of GBM. To identify the antigenic epitope(s) that may serve as targets for EGFRvIII-specific cytotoxic T lymphocytes (CTLs), the peptide sequence of EGFRvIII was screened with two software programs to predict candidate epitopes restricted by the major histocompatibility complex class I subtype HLA-A0201, which is the predominant subtype in most ethnic groups. Three predicted peptides were constructed and loaded to mature human DCs generated from peripheral blood monocytes. Autologous CD8+ T cells were stimulated in vitro with the EGFRvIII peptide-pulsed DCs. One of the three peptides was found to induce EGFRvIII-specific CTLs as demonstrated by IFN-γ production and cytotoxicity against HLA-A0201+ EGFRvIII transfected U87 glioma cells. These results suggest that vaccination with EGFRvIII peptide-pulsed DCs or adoptive transfer of in vitro elicited EGFRvIII-specific CTLs by EGFRvIII peptide-pulsed DCs are potential approaches to the treatment of glioma patients.

Original languageEnglish (US)
Pages (from-to)23-30
Number of pages8
JournalJournal of neuro-oncology
Volume76
Issue number1
DOIs
StatePublished - Jan 1 2006

    Fingerprint

Keywords

  • Dendritic cell vaccine
  • EGFRvIII
  • Glioma
  • HLAA0201
  • Immunotherapy

Cite this