| In general, viral vectors for cancer therapy can be divided into replication-defective or replication-competent, based on their reproductive capacities. Both types of vectors can target genes into neoplastic cells but only the latter show oncolytic potential. For example, a phase I clinical trial of p53 gene therapy was performed using a replication-defective adenovirus vector with wild-type p53 against malignant brain tumours. The vector was stereo tactically injected intratumorally via an implanted catheter. Treated tumour specimens were obtained and analysed afterwards. In all patients, exogenous p53 protein was detected within the nuclei of astrocytic tumour cells and transgene expression induced apoptosis of targeted cells.However, with the use of this replication-defective vector, transgene expression was limited to 5 mm from injection site. In contrast to replication-defective vectors, oncolytic viruses potentially offer increased replication, infectivity, and transgene expression.Adenoviruses are versatile, efficient and, in general, well suited for therapeutic gene delivery tasks. These vectors have the ability to grow as recombinant viruses to high titres and are capable of carrying genes of interest as insertions. Moreover, some of these viruses can infect, replicate, induce efficient transgene expression, and lyse neoplastic cells. In fact, these vehicles are currently being used in approximately one quarter of all trials for gene therapy. Taken together, all these highlights have made adenoviruses one of the most common transgene delivery systems for human gene therapy and a potentially useful therapeutic resource for treatment of brain tumours.Conditionally-replicative adenovirus or CRAd is a naturally selected or genetically engineered adenovirus that preferentially replicates in and kills tumour cells. This virus is ideally unable to replicate in normal cells. The main advantage of CRAd vectors is the fact that they can replicate in cancer cells. As such, culmination of every viral reproductive cycle leads to cell destruction and release of new viral particles. This progeny is once more able to infect neighbouring neoplastic cells, further enhancing the killing effect. The specificity of CRAds replication and transgene expression in target cells can be improved by strategies involving of adenoviral replication events. Some of the strategies used for the enhancement of viral tropism are deletion of viral genomic regions dispensable for replication in cancer cells with specific pathway alterations, facilitation of viral transduction in neoplastic cells, and transcriptional targeting of viral genes or transgenes using tumour-specific promoters.To investigate the anti-tumor properties of Apoptin of CAV. In this study, we evaluated the antitumoral effects on hepatoma cells (human BEL-7402 and mouse H22 cells) in vitro and in vivo. The in vitro anti-tumor effects of the recombiant adenovirus containing CAV Apoptin were evaluated by MTT staining, AO/EB staining, DAPI staining and Annexin V. The cell transduction properties of Apoptin expressed by the recombinant adenoviruses were detected by mitochondria trans-membrane potential assay and reactive oxygen species assay. We also observed the anti-tumor activity of the recombinant adenoviruses in vivo. The solid tumor model and the pulmonary metastasis model were established. The mean survival, the tumor growth, the suppression rate, the NK activity, the CTL activity and the cytokine levels of the animal models were evaluated. The results showed that the recombinant adenoviruses inhibited the hepatoma cell growth effectively by inducing apoptosis through mitochondrial pathway. Although the injection of the recombinant adenoviruses did not lead to complete elimination of the tumors, effective inhibition was observed in the established primary tumor model and the metastasis model.
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