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Identification of an HLA-A*0201-restrictive CTL epitope from MUC4 for applicable vaccine therapy.



Published on:2016-06-25   Views:169

Abstract

Recent research has indicated that MUC4plays an important role in the development of many tumors and may prove usefulas a novel cancer immunotherapy target. We aimed to identifyHLA-A*0201-restrictive cytotoxic T lymphocyte (CTL) epitopes of thecancer-associated antigen MUC4. The MUC4 sequence was scanned for immunogenicpeptides using HLA-binding prediction software. Dendritic cells (DCs) fromperipheral blood mononuclear cells (PBMCs) were induced by cytokines. Fivepossible CTL epitopes were selected by software analysis, synthesized, and usedto pulse mature DCs. The CD8(+) T cells from PBMCs from an HLA-A*0201 healthydonor were stimulated with autologous MUC4-peptide-loaded DCs and expanded invitro. T cell activation was assessed by ELISPOT, and cytotoxicity wasdetermined by (51)chromium ((51)Cr)-release assays. Our results show that CTLsinduced by peptide P01204 could lyse T2 cells pulsed with peptide P01204 andHCT-116 cells (MUC4(+), HLA-A2(+)). Compared with a control peptide, P01204increased the number of IFN-gamma producing T cells. Overall, these resultssuggest that P01204 is a novel HLA-A*0201-restrictive CTL epitope of thecancer-associated antigen MUC4. This will provide a foundation for thedevelopment of tumor-specific peptide vaccines.