Identification of EGFRvIII-derived CTL epitopes restricted by HLA A0201 for dendritic cell based immunotherapy of gliomas.
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-gamma 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.
Wu
An-hua
AH
Department of Neurosurgery, University of Minnesota Medical School, 2001 Sixth Street, Minneapolis, SE, MN 55455, USA.
Xiao
Jing
J
Anker
Lars
L
Hall
Walter A
WA
Gregerson
Dale S
DS
Cavenee
Webster K
WK
Chen
Wei
W
Low
Walter C
WC
D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes; D066246:ErbB Receptors / Q000235:genetics*; D005910:Glioma / Q000276:immunology* / Q000473:pathology; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D006801:Humans; D007167:Immunotherapy; D016219:Immunotherapy, Adoptive; D009000:Monocytes; D015183:Restriction Mapping; D012984:Software; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination
D000939:Epitopes; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D066246:ErbB Receptors