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: Nagoya University
• 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
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370667/
• 关键词: Helpes simplex virus thymidinekinase gene; Ganciclovir; Suicide gene therapy; Cationic liposome; Adenovirus vector; Oral Cancer; カチオニックリポソーム・アデノウイルスベクター複合体; 遺伝子導入効率

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.

腺病毒（Ad）载体由于其在基因转移中的效率而常用于基因治疗试验。然而，它们的使用受到减少转基因表达和降低重复载体施用效率的免疫应答的限制。本研究采用腺病毒载体结合阳离子脂质体（Ad-suctionalliposomes，Ad/SUV）体外转染4株人口腔癌细胞和1株鼠口腔癌细胞，观察其对人口腔癌细胞的基因转导效率和对肿瘤细胞的杀伤作用。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影响。在此基础上，我们在体内评价了Ad/SUV自杀基因治疗的抗肿瘤效果。与对照组相比，三次注射Ad/SUV均能抑制肿瘤生长。提示Ad/SUV重复给药对人口腔鳞癌有较好的抗肿瘤作用。

项目成果

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。

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