宫颈癌治疗性多肽疫苗的合成及其诱导细胞毒性T 淋巴细胞效应的研究

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (2): 200-203.

宫颈癌治疗性多肽疫苗的合成及其诱导细胞毒性T 淋巴细胞效应的研究

徐道华¹, 周晨慧², 夏永鹏³, 邱宗荫³, 贾正才⁴, 周伟⁴

¹广东医学院药理教研室, ²护理学院, 湛江 524023, 广东;
³重庆医科大学药学系, 重庆 400016;
⁴第三军医大学全军免疫学研究所, 重庆 400038

收稿日期:2006-08-19 修回日期:2007-01-12 出版日期:2007-02-26 发布日期:2020-10-27
作者简介:徐道华, 男, 博士, 副教授, 研究方向:肿瘤疫苗与新药开发。Tel:0759-2388588-3 E-mail: daohuax@yahoo.com.cn

Synthesis and cytotoxic T lymphocyte response in vivo of therapeutic vaccine against cervical cancer

XU Dao-hua¹, ZHOU Chen-hui², XIA Yong-peng³, QIU Zong-yin³, JIA Zheng-cai⁴, ZHOU Wei⁴

¹Department of Pharmacology, ²School of Nursing, Guangdong Medical College, Zhanjiang 524023, Guangdong, China;
³Department of Pharmacy, ChongqingUniversity of Medical Science, Chongqing 400016, China;
⁴Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, China

Received:2006-08-19 Revised:2007-01-12 Online:2007-02-26 Published:2020-10-27

摘要/Abstract

摘要： 目的: 设计并合成宫颈癌治疗性多肽疫苗, 并对其免疫学效应进行研究。方法: 以芴甲氧羰基固相法合成多肽, 用高效液相色谱分析多肽的纯度, 对所合成的多肽采用质谱进行鉴定, 用标准⁵¹Cr 释放试验检测各肽在HLA-A2 转基因鼠中诱导的表位特异性细胞毒性T 淋巴细胞活性。结果: 合成的多肽经纯化后纯度分别为86.5 %、81.8 %和98.5 %, 质谱分析各肽的相对分子质量分别为3 121 、2 580 和815, 与理论值相符。其在HLA-A2 转基因鼠中可诱导出强的表位特异性细胞毒性T 淋巴细胞活性。结论: 合成的多肽为目标肽, 将辅助性T 细胞表位及脂类分子构建于分子内部可提高细胞毒性T 淋巴细胞表位肽的免疫原性。

关键词: 子宫颈癌, 表位, 治疗性疫苗, 固相合成

Abstract: AIM: To design and synthesize the therapeutic vaccine against human cervical cancer and study its immunological effect.METHODS: The peptides were synthesized with solid phase strategies, purified with reverse phase HPLC and identified with mass spectrometry. Their immunological effects inducing(CTL) response were investigated in HLA-A2 transgenic mice, and the activity of specific CTL was measured by using a standard 4 h⁵¹Cr release assay.RESULTS: The purities of peptides were 86.5 %, 81.8 % and 98.5 %, respectively.Their molecular weights were 3 121, 2 580 and 815 respectively, which was the same as expected molecular mass.The therapeutic vaccine could induce strong specific CTL activity in HLA-A2 transgenic mice.CONCLUSION: The synthetical products are the target peptides.The combination of CTL and T helper epitope and lipid molecule can remarkably improve the immunogenicity of CTL peptide.

Key words: cervical cancer, epitope, therapeutic vaccine, solid phase synthesis

中图分类号:

R392.1
R967

徐道华, 周晨慧, 夏永鹏, 邱宗荫, 贾正才, 周伟. 宫颈癌治疗性多肽疫苗的合成及其诱导细胞毒性T 淋巴细胞效应的研究[J]. 中国临床药理学与治疗学, 2007, 12(2): 200-203.

XU Dao-hua, ZHOU Chen-hui, XIA Yong-peng, QIU Zong-yin, JIA Zheng-cai, ZHOU Wei. Synthesis and cytotoxic T lymphocyte response in vivo of therapeutic vaccine against cervical cancer[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(2): 200-203.

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