T cells redirected to EphA2 for the immunotherapy of glioblastoma

Mol Ther. 2013 Mar;21(3):629-37. doi: 10.1038/mt.2012.210. Epub 2012 Oct 16.


Outcomes for patients with glioblastoma (GBM) remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL)-13Rα2, epidermal growth factor receptor variant III (EGFRvIII), or human epidermal growth factor receptor 2 (HER2) has shown promise for the treatment of gliomas in preclinical models and in a clinical study (IL-13Rα2). However, targeting IL-13Rα2 and EGFRvIII is associated with the development of antigen loss variants, and there are safety concerns with targeting HER2. Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) has emerged as an attractive target for the immunotherapy of GBM as it is overexpressed in glioma and promotes its malignant phenotype. To generate EphA2-specific T cells, we constructed an EphA2-specific CAR with a CD28-ζ endodomain. EphA2-specific T cells recognized EphA2-positive glioma cells as judged by interferon-γ (IFN-γ) and IL-2 production and tumor cell killing. In addition, EphA2-specific T cells had potent activity against human glioma-initiating cells preventing neurosphere formation and destroying intact neurospheres in coculture assays. Adoptive transfer of EphA2-specific T cells resulted in the regression of glioma xenografts in severe combined immunodeficiency (SCID) mice and a significant survival advantage in comparison to untreated mice and mice treated with nontransduced T cells. Thus, EphA2-specific T-cell immunotherapy may be a promising approach for the treatment of EphA2-positive GBM.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Line, Tumor
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Glioblastoma / therapy*
  • Humans
  • Immunotherapy / methods*
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • K562 Cells
  • Male
  • Mice
  • Mice, SCID
  • Receptor, EphA2 / genetics*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Retroviridae / genetics
  • T-Lymphocytes / immunology*
  • Transduction, Genetic


  • Interleukin-2
  • Interferon-gamma
  • ERBB2 protein, human
  • Receptor, EphA2
  • Receptor, ErbB-2