Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.
Adv Cancer Res. 2012;115:39-67. doi: 10.1016/B978-0-12-398342-8.00002-1.
Cancer gene therapy approaches have benefited greatly from the utilization of molecular-based therapeutics. Of these, adenovirus-based interventions hold much promise as a platform for targeted therapeutic delivery to tumors. However, a barrier to this progression is the lack of native adenovirus receptor expression on a variety of cancer types. As such, any adenovirus-based cancer therapy must take into consideration retargeting the vector to nonnative cellular surface receptors. Predicated upon the knowledge gained in native adenovirus biology, several strategies to transductionally retarget adenovirus have emerged. Herein, we describe the biological hurdles as well as strategies utilized in adenovirus transductional targeting, covering the progress of both adapter-based and genetic manipulation-based targeting. Additionally, we discuss recent translation of these targeting strategies into a clinical setting.
癌症基因治疗方法极大地受益于基于分子的治疗方法的利用。在这些方法中,腺病毒为基础的干预措施作为一种将靶向治疗递送到肿瘤的平台具有很大的潜力。然而,这一进展的障碍是缺乏各种癌症类型的天然腺病毒受体表达。因此,任何基于腺病毒的癌症治疗都必须考虑将载体重新靶向到非天然的细胞表面受体。基于对天然腺病毒生物学的了解,已经出现了几种将腺病毒转导性重新靶向的策略。在此,我们描述了在腺病毒转导靶向中遇到的生物学障碍和所利用的策略,涵盖了基于适配器和遗传操作的靶向的进展。此外,我们还讨论了这些靶向策略最近在临床环境中的转化。