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Development of New diagnostic methods and treatments against EB virus as a target in nasal NK/T cell lymphoma

开发针对 EB 病毒作为鼻 NK/T 细胞淋巴瘤靶标的新诊断方法和治疗方法

基本信息

批准号：
17390455
负责人：
HARABUCHI Yasuaki
金额：
$ 6.89万
依托单位：
Asahikawa Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

(1) Virological analysisWe analyzed nasal NK/T cell lymphoma cell line to investigate the role of cytokines by cDNA microarray. IL-9 was expressed in EB virus positive nasal NK/T cell lymphoma cell line but not negative cell lines. In addition, it seems that IL-9 has contributed for the cell proliferation by autocrine mechanism in the cell line. s.We analyzed gene mutation of LMP1 and LMP2A in nasal NK/T cell lymphoma tissues. Deletion of LMP1 and mutations of LMP2A were discovered in the tissuesWe analyzed chemokines in nasal NK/T cell lymphoma cell line by the antibody array. IP-10 was expressed in nasal NK/T cell lymphoma cell line. In addition, it seems that IP-10 has contributed for the cell migration by autocrine mechanism.(2) Development of new diagnostic methodsWe developed a real time PCR method to measure EBV DNA load in sera of nasal NK/T cell lymphoma patients. Serum EBV DNA load was useful for diagnosis of this disease and to predict patient's prognosis and recurrence.(3) Development of new treatment methodsIntra-arterial chemotherapy and radiotherapy we developed was useful and safety to treat nasal NK/T cell lymphoma.Helper T lymphocytes were developed using LMP1 peptides. The T cells recognize a peptide (LMP1 159-175) with promiscuous epitopes of LMP1 and restricted HLA-DR9, DR53 and DR15. In addition, the T cells killed lymphoma cells.

(1)病毒学分析采用基因芯片技术对鼻NK/T细胞淋巴瘤细胞株进行了细胞因子分析。IL-9在EB病毒阳性的鼻NK/T细胞淋巴瘤细胞系中表达，而在EB病毒阴性的鼻NK/T细胞淋巴瘤细胞系中不表达。此外，IL-9在细胞系中似乎通过自分泌机制促进细胞增殖。分析鼻NK/T细胞淋巴瘤组织中LMP 1和LMP 2A基因突变情况。结果发现，鼻NK/T细胞淋巴瘤细胞株中存在LMP 1基因缺失和LMP 2A基因突变。IP-10在鼻NK/T细胞淋巴瘤细胞系中表达。此外，IP-10似乎通过自分泌机制促进细胞迁移。(2)本研究建立了一种真实的时间PCR方法，用于检测鼻NK/T细胞淋巴瘤患者血清中EB病毒DNA载量。血清EBVDNA载量对本病的诊断、预后及复发有一定的参考价值。(3)新的治疗方法的开发我们开发的动脉内化疗和放疗治疗鼻NK/T细胞淋巴瘤是有效和安全的。T细胞识别具有LMP 1和限制性HLA-DR 9、DR 53和DR 15的混杂表位的肽（LMP 1159 -175）。此外，T细胞杀死淋巴瘤细胞。