Hasegawa Kosei, Noguchi Yuji, Koizumi Fumihito, Uenaka Akiko, Tanaka Motoyuki, Shimono Michihide, Nakamura Hideo, Shiku Hiroshi, Gnjatic Sacha, Murphy Roger, Hiramatsu Yuji, Old Lloyd J, Nakayama Eiichi
Department of Immunology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Clin Cancer Res. 2006 Mar 15;12(6):1921-7. doi: 10.1158/1078-0432.CCR-05-1900.
PURPOSE: NY-ESO-1 belongs to a class of cancer/testis antigens and has been shown to be immunogenic in cancer patients. We synthesized a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein (CHP/ESO) and investigated the in vitro stimulation of CD8 and CD4 T cells from peripheral blood mononuclear cells in healthy donors with autologous CHP/ESO-loaded dendritic cells as antigen-presenting cells. EXPERIMENTAL DESIGN: In vitro stimulation of CD8 or CD4 T cells was determined by IFNgamma ELISPOT assays against autologous EBV-B cells infected with vaccinia/NY-ESO-1 recombinant virus or wild-type vaccinia virus as targets and by ELISA measuring secreted IFNgamma. RESULTS: NY-ESO-1-specific CD8 and CD4 T cells were induced. In a donor expressing HLA-A2, CD8 T cells stimulated with CHP/ESO-loaded dendritic cells recognized naturally processed NY-ESO-1(157-165), an HLA-A2-binding CD8 T cell epitope. NY-ESO-1 CD4 T cells were Th1-type. We identified a new HLA-DR15-binding CD4 T cell epitope, NY-ESO-1(37-50). CONCLUSIONS: These findings indicate that CHP/ESO is a promising polyvalent cancer vaccine targeting NY-ESO-1.
目的：NY - ESO - 1属于癌胚抗原类，已证实在癌症患者中具有免疫原性。我们合成了一种含胆固醇的疏水化支链淀粉与NY - ESO - 1蛋白的复合物（CHP/ESO），并以负载自体CHP/ESO的树突状细胞作为抗原呈递细胞，研究其对健康供体外周血单个核细胞中CD8和CD4 T细胞的体外刺激作用。 实验设计：通过针对感染痘苗/NY - ESO - 1重组病毒或野生型痘苗病毒的自体EBV - B细胞作为靶标的IFNγ ELISPOT检测，以及通过ELISA检测分泌的IFNγ，来确定CD8或CD4 T细胞的体外刺激情况。 结果：诱导出了NY - ESO - 1特异性的CD8和CD4 T细胞。在一名表达HLA - A2的供体中，用负载CHP/ESO的树突状细胞刺激的CD8 T细胞识别天然加工的NY - ESO - 1(157 - 165)，这是一个与HLA - A2结合的CD8 T细胞表位。NY - ESO - 1 CD4 T细胞为Th1型。我们鉴定出了一个新的与HLA - DR15结合的CD4 T细胞表位，NY - ESO - 1(37 - 50)。 结论：这些发现表明CHP/ESO是一种有前景的靶向NY - ESO - 1的多价癌症疫苗。
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