Yorkshire Cancer Research Unit, Dept of Biology, University of York, York YO10 5DD, United Kingdom.
J Invertebr Pathol. 2011 Jul;107 Suppl:S59-70. doi: 10.1016/j.jip.2011.05.006.
Prostate cancer is the most commonly diagnosed cancer in ageing men in the western world. While the primary cancers can be treated with androgen ablation, radiotherapy and surgery, recurrent castration resistant cancers have an extremely poor prognosis, hence promoting research that could lead to a better treatment. Targeted therapeutic gene therapy may provide an attractive option for these patients. By exploiting the natural ability of viruses to target and transfer their genes into cancer cells, either naturally or after genetic manipulation, new generations of biological control can be developed. In this review we present the advantages and practicalities of using baculovirus as a vector for prostate cancer gene therapy and provide evidence for the potential of the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) as a safer alternative vehicle for targeting cancer cells. Strategies to target baculovirus binding specifically to prostate cell surfaces are also presented. The large insertion capacity of baculoviruses also permits restricted, prostate-specific gene expression of therapeutic genes by cloning extended human transcriptional control sequences into the baculovirus genome.
在西方世界,前列腺癌是老年男性中最常见的癌症。虽然原发癌症可以通过雄激素剥夺、放疗和手术治疗,但复发性去势抵抗性癌症预后极差,因此需要研究新的治疗方法。靶向治疗基因治疗可能为这些患者提供一种有吸引力的选择。通过利用病毒靶向和将其基因转移到癌细胞中的自然能力,无论是自然发生的还是经过基因改造的,都可以开发新一代的生物控制。在这篇综述中,我们介绍了使用杆状病毒作为前列腺癌基因治疗载体的优势和实用性,并提供了杆状病毒 Autographa californica 多角体病毒 (AcMNPV) 作为靶向癌细胞更安全替代载体的潜力的证据。我们还提出了使杆状病毒特异性结合前列腺细胞表面的策略。杆状病毒的大容量插入能力也允许通过将扩展的人类转录控制序列克隆到杆状病毒基因组中来限制前列腺特异性表达治疗基因。