Elsevier

Neoplasia

Volume 7, Issue 8, August 2005, Pages 717-722
Neoplasia

EphA2 as a Glioma-Associated Antigen: A Novel Target for Glioma Vaccines1

https://doi.org/10.1593/neo.05277Get rights and content
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open access

Abstract

EphA2 is a receptor tyrosine kinase, is frequently overexpressed in a wide array of advanced cancers. We demonstrate in the current study that the EphA2 protein is restrictedly expressed in primary glioblastoma multiforme, anaplastic astrocytoma tissues in comparison to normal brain tissues. To evaluate the possibility of targeting EphA2 in glioma vaccine strategies, we stimulated human leukocyte antigen (HLA) A2+ peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, glioma patients with autologous dendritic cells (DCs) loaded with synthetic EphA2$$3_$91 peptide (TLADFDPRV), which has previously been reported to induce interferon-δ in HLAA2+ PBMCs. Stimulated PBMCs demonstrated antigenspecific cytotoxic T lymphocyte (CTL) responses as detected by specific lysis of T2 cells loaded with the EphA2883 peptide as well as HLA-A2+ glioma cells, SNB19, U251, that express EphA2. Furthermore, in vivo immunization of HLA-A2 transgenic HHD mice with the EphA2883-891 peptide resulted in the development of an epitope-specific CTL response in splenocytes, despite the fact that EphA2883-891 is an autoantigen in these mice. Taken together, these data suggest that EphA2883-891 may be an attractive antigen epitope for molecularly targeted glioma vaccines.

Keywords

EphA2
glioma
cancer vaccine
cytotoxic T lymphocytes
human leukocyte antigen (HLA) A2

Abbreviations

CTL
cytotoxic T lymphocyte
DC
dendritic cell
E/T ratio
effector-to-target ratio
HLA
human leukocyte antigen
IL
interleukin
PBMC
peripheral blood mononuclear cell

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1

This work was supported by P01 NS40923 (I.F.R, H.O.), a Clinical Scientist Development Award from the Doris Duke Charitable Foundation (H.O.), a 21st Century Scientist Award from the James S. McDonnell Foundation (H.O.), the Copel, Fund of the Pittsburgh Foundation (H.O., NX.).