Combination epidermal growth factor receptor variant III peptide-pulsed dendritic cell vaccine with miR-326 results in enhanced killing on EGFRvIII-positive cells
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Jianlong Li1,2,3,*, Feng Wang1,3,*, Guangzhi Wang1, Ying Sun1,3, Jinquan Cai1,2,3, Xing Liu3,4, Junhe Zhang1,3, Xiaoyan Lu5, Yongli Li1,3, Meng Chen1, Lingchao Chen6,3, Chuanlu Jiang1,2,3
1Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
2Neuroscience Institute, Heilongjiang Academy of Medical Sciences, Harbin 150086, China
3Chinese Glioma Cooperative Group (CGCG), Beijing 100050, China
4Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China
5Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
6Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China
*These authors are contributed equally to this work
Chuanlu Jiang, email: jc[email protected]
Lingchao Chen, email: [email protected]
Keywords: EGFRvIII, dendritic cell vaccine, miR-326, hedgehog signalling pathway, TGF-β1
Received: October 04, 2016 Accepted: February 06, 2017 Published: February 17, 2017
The mutant Type III variant of epidermal growth factor receptor (EGFRvIII) is present in approximately one-third of glioblastoma (GBM) patients. It is never found in normal tissues; therefore, it represents a candidate target for GBM immunotherapy. PEPvIII, a peptide sequence from EGFRvIII, was designed to represent a target of glioma and is presented by MHC I/II complexes. Dendritic cells (DCs) have great potential to sensitize CD4+ T and CD8+ T cells to precisely target and eradicate GBM. Here, we show that PEPvIII could be loaded by DCs and presented to T lymphocytes, especially PEPvIII-specific CTLs, to precisely kill U87-EGFRvIII cells. In addition to inhibiting proliferation and inducing the apoptosis of U87-EGFRvIII cells, miR-326 also reduced the expression of TGF-β1 in the tumour environment, resulting in improved efficacy of T cell activation and killing via suppressing the SMO/Gli2 axis, which at least partially reversed the immunosuppressive environment. Furthermore, combining the EGFRvIII-DC vaccine with miR-326 was more effective in killing U87-EGFRvIII cells compared with the administration of either one alone. This finding suggested that a DC-based vaccine combined with miR-326 may induce more powerful anti-tumour immunity against GBM cells that express a relevant antigen, which provides a promising approach for GBM immunotherapy.
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