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

腺病毒载体因其在基因转移方面的有效性而被广泛应用于基因治疗试验中。然而，它们的使用受到免疫反应的限制，这些免疫反应减少了转基因表达，降低了重复给药的效率。在本研究中，我们证明了腺病毒载体与阳离子脂质体(Ad/SUV)的偶联(Ad/SUV)在体外提高了自杀基因治疗对4种人口腔癌细胞和1种小鼠鳞状细胞癌细胞的基因转导效率和对肿瘤细胞的杀伤作用，最佳的Ad-SUV比例为10~6pfu/1-mol。有趣的是，我们还证明了在体外，Ad/SUV可以保护Ad载体免受中和抗体的攻击。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对肿瘤生长均有抑制作用。我们的结果表明，重复给药对口腔鳞状细胞癌有更强的抗肿瘤作用。

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.