Jayawardena Nadishka, Poirier John T, Burga Laura N, Bostina Mihnea
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Department of Medicine and Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Oncolytic Virother. 2020 Mar 6;9:1-15. doi: 10.2147/OV.S186337. eCollection 2020.
Oncolytic viruses (OVs) are replication competent agents that selectively target cancer cells. After penetrating the tumor cell, viruses replicate and eventually trigger cell lysis, releasing the new viral progeny, which at their turn will attack and kill neighbouring cells. The ability of OVs to self-amplify within the tumor while sparing normal cells can provide several advantages including the capacity to encode and locally produce therapeutic protein payloads, and to prime the host immune system. OVs targeting of cancer cells is mediated by host factors that are differentially expressed between normal tissue and tumors, including viral receptors and internalization factors. In this review article, we will discuss the evolution of oncolytic viruses that have reached the stage of clinical trials, their mechanisms of oncolysis, cellular receptors, strategies for targeting cancers, viral neutralization and developments to bypass virus neutralization.
溶瘤病毒(OVs)是能够在肿瘤细胞中进行复制的介质,可选择性地靶向癌细胞。侵入肿瘤细胞后,病毒进行复制并最终引发细胞裂解,释放出新的子代病毒,这些子代病毒又会转而攻击并杀死邻近细胞。溶瘤病毒在肿瘤内自我扩增同时不损伤正常细胞的能力具有诸多优势,包括编码和局部产生治疗性蛋白有效载荷的能力,以及激活宿主免疫系统的能力。溶瘤病毒对癌细胞的靶向作用是由正常组织和肿瘤之间差异表达的宿主因子介导的,包括病毒受体和内化因子。在这篇综述文章中,我们将讨论已进入临床试验阶段的溶瘤病毒的发展历程、它们的溶瘤机制、细胞受体、靶向癌症的策略、病毒中和作用以及绕过病毒中和作用的进展。