Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1100 S. Grand Blvd, St. Louis, MO 63104, USA.
Viruses. 2010 Sep;2(9):1844-1866. doi: 10.3390/v2091844. Epub 2010 Aug 27.
Oncolytic adenovirus (Ad) vectors present a new modality to treat cancer. These vectors attack tumors via replicating in and killing cancer cells. Upon completion of the vector replication cycle, the infected tumor cell lyses and releases progeny virions that are capable of infecting neighboring tumor cells. Repeated cycles of vector replication and cell lysis can destroy the tumor. Numerous Ad vectors have been generated and tested, some of them reaching human clinical trials. In 2005, the first oncolytic Ad was approved for the treatment of head-and-neck cancer by the Chinese FDA. Oncolytic Ads have been proven to be safe, with no serious adverse effects reported even when high doses of the vector were injected intravenously. The vectors demonstrated modest anti-tumor effect when applied as a single agent; their efficacy improved when they were combined with another modality. The efficacy of oncolytic Ads can be improved using various approaches, including vector design, delivery techniques, and ancillary treatment, which will be discussed in this review.
溶瘤腺病毒(Ad)载体为癌症治疗提供了一种新的方式。这些载体通过在肿瘤细胞中复制并杀死肿瘤细胞来攻击肿瘤。在载体复制周期完成后,受感染的肿瘤细胞裂解并释放能够感染相邻肿瘤细胞的子代病毒颗粒。载体的反复复制和细胞裂解循环可以破坏肿瘤。已经产生并测试了许多 Ad 载体,其中一些已经进入了人体临床试验。2005 年,中国 FDA 批准了第一种溶瘤腺病毒用于治疗头颈部癌症。溶瘤 Ad 已被证明是安全的,即使静脉内注射高剂量载体也没有报告严重的不良反应。当作为单一药物应用时,这些载体显示出适度的抗肿瘤作用;当与另一种方式联合使用时,其疗效得到改善。通过各种方法可以提高溶瘤 Ad 的疗效,包括载体设计、递送技术和辅助治疗,这将在本综述中讨论。