The highest degree of EphA2 expression among tumors is inspected most commonly in metastatic lesions, recommending that EphA2 may represent a high-priority target for immunotherapy, particularly in patients with advanced stage or metastatic cancer. Yamaguchi et al showed that some patients with renal cell carcinoma exhibited both CD8-positive and CD4-positive T Cell responses to novel, EphA2-derived epitopes and that was useful for predicting disease status and outcome as immunomonitoring targets(145). Shinjiro et al investigated the efficacy of vaccination based on DCs pulsed with EphA2-derived peptides(Eph-DCs) in a murine colon and liver cancer model(145,157). Eph-DCs immunization inhibited EphA2 positive MC38 cell-induced tumor growth, but EphA2-DCs vaccination had no impact on EphA2 negative BL6 cell-induced tumor growth(145). These results also supported the therapeutic potential Eph-DC based vaccines(145). But, the clinical application of DC-based vaccine continues limited by several components, as well as regulating DCs in a highly activated state, limited time period and lack of coincidental functional alterations or cytotoxicity(148,149). To augment T cell responses to weak tumor antigens, Chen et al developed a novel vaccine using EphA2 epitope fused with LIGHT plasmid serves as a promising approach for glioma treatment(150). Mayumi et al investigated HSP90 inhibitors, such as 17-DMAG (alvespimycin) for enhanced EphA2 reduction by stimulated EphA2 overexpression tumor cell recognition through specific CD+8 T cell immunoreactivity. These findings suggested that 17-DMAG functions as an immunotherapeutic in the framework of vaccines directing EphA2(158,159Mang li et al determined that ephrin A1–PE38-GM-CSF have high efficacy in the activation of the dendritic cells could facilitate the advancement of in vivo dendritic-cell vaccines for the treatment of glioma through a specific local antitumor immune response and a systemic immunotherapeutic effect(activation). Recently, a cocktail of three glioma-associated antigens (EphA2, IL13R?2, surviving) in combination with poly-ICLC based vaccination was developed and clinical trial proved safety to treated in pediatric patients with high-grade gliomas (HGGs)(160,161,162,163).