肝素酶CTL表位负载的树突状细胞疫苗体外抗肿瘤免疫效应研究

陈婷; 汤旭东; 万瑛; 房殿春; 梁光萍; 陈陵; 余松涛; 熊震; 师红雷; 罗元辉; 杨仕明

doi:10.3969/j.issn.1672-2353.2008.01.004

肝素酶CTL表位负载的树突状细胞疫苗体外抗肿瘤免疫效应研究

1.
第三军医大学西南医院全军消化病研究所;
2.
第三军医大学基础部全军免疫学研究所;
3.
第三军医大学西南医院烧伤、创伤、复合伤国家重点实验室,重庆,400038

基金项目: 国家自然科学基金

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中图分类号: R730.5
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- 发布日期: 2008-07-13

Heparanase epitope peptide-pulsed DCs elicit immune responses against various tumors in vitro

摘要

摘要: 目的研究肝素酶(Hpa)多肽疫苗体外能否诱发肝素酶特异性CTL反应,为肝素酶多肽疫苗的临床应用提供理论依据.方法　5条HLA-A2限制性肝素酶抗原表位[Hpa(525-533)(PAFSYSFFV)、Hpa(353-361)(PLLSDTFAA)、Hpa(277-285)(KMLKSFLKA)、Hpa(400-408)(PLPDYWLSL)、Hpa(405-413)(WLSLLFKKL)]分别负载正常人外周血来源(PBMC)的树突状细胞(DC),诱导肝素酶特异性细胞毒T淋巴细胞(CTL),采用4 h标准51Cr释放实验检测上述CTL对不同肿瘤细胞的免疫杀伤效应,采用ELISPOT方法检测肝素酶表位肽负载的DC疫苗刺激的效应细胞IFN-γ的释放.结果 5条肝素酶多肽表位中,只有Hpa(525-533)、Hpa(277-285)和Hpa(405-413)体外可以诱导肝素酶表位特异性CTL反应,对Hpa阳性且HLA-A2阳性的KATO-S胃癌细胞、U2OS骨肉瘤细胞、SW480结肠癌细胞具有明显的杀伤效应.对HLA-A2阴性的HepG2肝癌细胞和Hpm阴性的MCF-7乳腺癌细胞不具有杀伤效应,但对转染了HLA-A2的HepG2细胞和转染了肝素酶质粒的MCF-7细胞恢复杀伤效应,对自体淋巴细胞不具有杀伤效应,进一步研究表明,Hpa(525-533)、Hpa(277-285)和Hpa(405-413)表位肽可以促进CTL细胞IFN-γ的释放.结论人肝素酶特异性抗原表位Hpa(525-533)、Hpa(277-285)、Hpa(405-413)不仅能激发机体特异性的抗肿瘤效应,而且还能诱导一个非特异性抗肿瘤的良性循环,这种肝素酶多肽疫苗具有广谱、高效、特异、安全的优点,为肝素酶表位多肽疫苗的临床应用提供了理论依据.
- 肝素酶 /
- CTL表位 /
- 树突状细胞 /
- 肿瘤疫苗

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文章访问数: 306
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肝素酶CTL表位负载的树突状细胞疫苗体外抗肿瘤免疫效应研究

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出版历程

Heparanase epitope peptide-pulsed DCs elicit immune responses against various tumors in vitro

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