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Identification of EGFRvIII-derived CTL Epitopes Restricted by HLA A0201 for Dendritic Cell Based Immunotherapy of Gliomas

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Summary

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.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Minnesota Medical School, 2001 Sixth Street, Minneapolis, SE, MN 55455

    An-hua Wu, Jing Xiao, Lars Anker, Walter A. Hall & Walter C. Low

  2. Department of Ophthalmology, University of Minnesota Medical School, 2001 Sixth Street, Minneapolis, SE, MN 55455

    Dale S. Gregerson

  3. Department of Pediatrics, University of Minnesota Medical School, 420 Delaware Street, Minneapolis, SE, MN 55455

    Wei Chen

  4. The Cancer Center, University of Minnesota Medical School, 420 Delaware Street, Minneapolis, SE, MN 55455

    Walter A. Hall, Wei Chen & Walter C. Low

  5. The Ludwig Institute for Cancer Research, Center for Molecular Genetics, Cancer Center and Department of Medicine, University of California, San Diego, CA, 92093

    Webster K. Cavenee

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  1. An-hua Wu
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  2. Jing Xiao
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  3. Lars Anker
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  7. Wei Chen
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  8. Walter C. Low
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Correspondence to Walter C. Low.

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Wu, Ah., Xiao, J., Anker, L. et al. Identification of EGFRvIII-derived CTL Epitopes Restricted by HLA A0201 for Dendritic Cell Based Immunotherapy of Gliomas. J Neurooncol 76, 23–30 (2006). https://doi.org/10.1007/s11060-005-3280-7

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  • DOI: https://doi.org/10.1007/s11060-005-3280-7

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