Centre for Gene Therapeutics, McMaster University, Hamilton, ON, Canada L8N 3Z5.
Hum Gene Ther. 2011 Sep;22(9):1053-60. doi: 10.1089/hum.2010.227. Epub 2011 May 19.
The efficient delivery of viral vectors to tumors is an active area of investigation. A number of barriers exist that must be overcome to achieve good penetration of vectors into tumors and distribution of their effects throughout the tumor mass. Replicating oncolytic viruses have the advantage of being able to amplify the initial dose, but progeny virus are prevented from spreading because of a dense mass of tightly packed cells with a dense extracellular matrix, admixed normal stromal cells, and high interstitial pressure. Although intratumoral injection may ensure initial delivery the distribution achieved by intravenous administration may be superior and come with beneficial bystander damage to the tumor vasculature. Strategies to enhance intravenous delivery and subsequent spread of these vectors within tumors are being developed by a number of groups. Achieving the goal of efficient penetration and spread of viruses within solid tumors is a necessary prerequisite to significant improvements in virus-vectored therapy of solid tumors.
病毒载体向肿瘤的有效递呈是一个活跃的研究领域。为了实现载体对肿瘤的良好穿透和其效果在肿瘤块中的分布，必须克服许多障碍。复制型溶瘤病毒具有能够扩增初始剂量的优势，但由于致密的紧密堆积细胞、致密的细胞外基质、混杂的正常基质细胞和高细胞间质压力，子代病毒无法扩散。尽管肿瘤内注射可以确保初始递呈，但静脉内给药所达到的分布可能更优，并且对肿瘤血管产生有益的旁观者损伤。许多研究小组正在开发增强这些载体在肿瘤内的静脉内递呈和随后扩散的策略。实现病毒在实体瘤内有效穿透和扩散的目标是显著改善病毒载体治疗实体瘤的必要前提。
