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Study of the gene therapy using virus vector-liposome complex for head and neck cancer

Study of the gene therapy using virus vector-liposome complex for head and neck cancer
病毒载体-脂质体复合物治疗头颈癌基因治疗的研究
批准号:
14370667
负责人:
IWAI Tohnai
金额:
$5.18万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2002
资助国家:
日本
项目状态:
已结题
起止时间:
2002 至 2003

项目摘要

项目成果

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中文摘要
翻译
腺病毒(Ad)载体因其在基因转移方面的有效性而被广泛用于基因治疗试验。然而,它们的使用受到免疫反应的限制,这些免疫反应会减少转基因表达和降低重复载体施用的效率。在本研究中,我们证实了腺病毒载体结合阳离子脂质体(Ad/SUV)在体外对4个人口腔和1个小鼠鳞癌细胞株进行自杀基因治疗,提高了基因转导效率和肿瘤细胞杀伤效果,Ad载体与1□mol的最佳Ad-SUV比为10^6 pfu。有趣的是,我们还证明了Ad/SUV在体外保护Ad载体免受中和抗体的侵害。在这些结果的基础上,我们在体内评估了自杀基因治疗Ad/SUV的抗肿瘤效果。与对照组相比,三次注射Ad/SUV对肿瘤生长有抑制作用。提示反复给药Ad/SUV对人口腔鳞状细胞癌具有更强的抗肿瘤作用。
英文摘要
Adenovirus (Ad) vectors are commonly used in gene therapy trials because of their efficiency in gene transfer. However, their use is limited by immune responses that reduce transgene expression and decrease the efficiency of repeated vector administration. In this study, we demonstrated that adenovirus vector conjugated with cationic liposomes (Ad/SUV) increased gene transduction efficiency and tumor cell killing effect with suicide gene therapy for four human oral and one murine squamous cell carcinoma cell lines in vitro, and optimal Ad-SUV ratio was 10^6 pfu of Ad vector with 1 □mol. SUV Interestingly, we also demonstrated that Ad/SUV shields Ad vector from neutralizing antibodies in vitro. On the basis of these results, we evaluated anti-tumor effect with suicide gene therapy with Ad/SUV in vivo. Three injection of Ad/SUV showed the inhibition of tumor growth compared with control in vivo. Our results suggested that we would obtain more anti-tumor effect for human oral squamous cell carcinoma with repeated administration of Ad/SUV.
期刊论文(4)
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科研奖励(0)
会议论文
Hirokazu Fukuhara: "Improvement of transduction efficiency of recombinant adenovirus vector conjugated with cationic liposome for human oral squamous cell carcinoma cell lines"Oral Oncology. 39. 601-609 (2003)
Hirokazu Fukuhara:“与阳离子脂质体缀合的重组腺病毒载体对人口腔鳞状细胞癌细胞系的转导效率的提高”口腔肿瘤学。
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通讯作者:
H.Fukuhara, Y.Hayashi, N.Yamamoto, T.Fukui, M.Nishikawa, K.Mitsudo, I.Tohnai, M.Ueda, M.Mizuno, J.Yoshida: "Improvement of transduction efficiency of recombinant adenovirus vector conjugated with cationic liposome for human oral squamous cell carcinoma ce
H.Fukuhara、Y.Hayashi、N.Yamamoto、T.Fukui、M.Nishikawa、K.Mitsudo、I.Tohnai、M.Ueda、M.Mizuno、J.Yoshida:“提高重组腺病毒载体缀合的转导效率
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