Development of the gene therapy for the malignant brain tumor using the oncolytic herpes virus vector

我们开发的载体被命名为HSV1yCD和溶瘤载体。该病毒载体最独特的特点是可以选择性地感染和溶解肿瘤细胞，而不能溶解正常细胞。换句话说，它可以选择性地摧毁渗透到正常大脑中的肿瘤细胞。本课题的目的是收集溶瘤病毒基因治疗脑肿瘤的实验数据，为今后的临床基因治疗提供依据。直到2003年，我们已经证实HSV1yCD载体可以感染肿瘤细胞，并高效地产生胞嘧啶脱氨酶，将5-FC转化为5-FU。我们也证实了5-FU是体外抗胶质瘤细胞的有效药物。2004年，我们对使用HSV1yCD的体内研究提出了挑战。将9L和C6胶质瘤细胞注射到大鼠脑内，然后将HSV1yCD注射到脑内。考察了几种实验条件，确定了最佳实验方法。我们检测了HSV1yCD的感染效果和溶瘤活性。与对照载体相比，HSV1yCD能有效地杀伤肿瘤细胞。我们还检测了注射肿瘤细胞并随后用HSV1yCD和5-FC治疗的大鼠的存活率。结论HSV1yCD可能是治疗脑肿瘤的有效载体。虽然还需要进一步的研究，但HSV1yCD有望成为未来治疗脑肿瘤的临床工具。

The vector which we have developed was termed HSV1yCD and an oncolytic vector. The most unique character of this virus vector was that it can selectively infect and lyse the tumor cell but not lyse the normal cell. In other words, it can selectively destroy the tumor cells infiltrating into the normal brain. The purpose of this project was to collect the experimental data about the oncolytic virus gene therapy against the brain tumor and to utilize the data for the future clinical gene therapy. Until the year 2003 we have confirmed that HSV1yCD vector can infect the tumor cells and efficiently produce cytosine deaminase which can convert 5-FC to 5-FU. We also have confirmed that 5-FU was effective drug against glioma cells in vitro. In the year 2004 we have challenged the in vivo study using the HSV1yCD. 9L and C6 glioma cells were injected into the rat brains and subsequently the HSV1yCD was injected into the brain. Several experimentally condition has been examined and the optimal experimental methods were established. We have examined the infectious efficacy of the HSV1yCD and the oncolytic activity. Compared the contol vector, HSV1yCD could efficiently destroy the tumor cells. We also have examined the survival rate of the rats injected the tumor cells and subsequently treated with the HSV1yCD and 5-FC. We concluded the HSV1yCD may be a effective vector for the treatment of the brain tumor. Although a further investigation should be required, the HSV1yCD could be a promising tool for the future clinical tool against the brain tumor.