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EB病毒潜伏膜蛋白2A转染树突状细胞诱导特异性CTL杀伤鼻咽癌的体外、体内研究
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摘要
鼻咽癌(nasopharyngeal carcinoma,NPC)为上皮来源的恶性肿瘤,高发于东南亚及我国华南地区。鼻咽癌通常不亦采用手术切除,放、化疗虽然对其有效,然而对部分病例并不能完全杀灭、清除肿瘤细胞,尤其是转移病灶和循环血液中的肿瘤细胞更难清除,并且治疗产生的副作用可进一步损伤机体免疫系统功能,部分患者易复发和转移。籍此,寻求有效的免疫治疗方法是鼻咽癌治疗研究的热点问题。
     研究证实,机体抗肿瘤效应主要以细胞毒性T细胞(cytotoxicity T lymphocyte,CTL)介导的细胞免疫为主,肿瘤抗原必须经过抗原递呈细胞(antigen presenting cell,APC)加工、处理,才能激发有效的抗肿瘤免疫反应。树突状细胞(dendritic cell,DC)是目前发现功能最强、唯一能激活初始型T细胞并诱导机体产生初次免疫应答的APC。越来越多的证据表明,应用各种形式的抗原修饰DC,可在体内外诱导出特异性CTL,激发出有效的抗肿瘤免疫效应。近期体外、动物及临床研究已显示出DC在肿瘤治疗中的巨大应用前景。
     进行CTL为基础的治疗前提是需选择一合适的肿瘤靶抗原。研究已证实EB病毒(Epstein-Barr virus,EBV)与鼻咽癌关系密切,该病毒是比较明确的DNA肿瘤病毒,近年血清流行病学、肿瘤EB病
Nasopharyngeal carcinoma (NPC) is a malignant tumor derived from the epithelial cells and occurs mainly in the Southeast Asia and South of China. NPC is usually difficult to be removed by surgery. Although radiotherapeutic and chemotherapeutic methods are effective for NPC, they could not eliminate tumor cells completely, especially those in circulatory systems and metastatic focuses. The immunologic function of the patients could also be damaged by these conventional methods during treatment. Relapse and metastasis of tumor occur usually in some NPC cases. Therefore, it is critically important to develop an immuno-therapeutic method for NPC.
    It has been demonstrated that the cellular immunity, especially cytotoxic T cells (CTL) response, plays an important role in the immune response against tumor. Antigen presentation is critical for the initiation of adoptive immune responses. Dendritic cells (DC) are known as the most powerful and the only antigen-presenting cells (APC), which are capable of activating naive T cells and initiating primary immune response. More and more studies prove that DC pulsed with various
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