Chaurasiya Shyambabu, Fong Yuman, Warner Susanne G
Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA.
Cancers (Basel). 2020 Jun 26;12(6):1699. doi: 10.3390/cancers12061699.
The field of oncolytic virotherapy has seen remarkable advancements in last two decades, leading to approval of the first oncolytic immuno-virotherapy, Talimogene Laherparepvec, for the treatment of melanoma. A plethora of preclinical and clinical studies have demonstrated excellent safety profiles of other oncolytic viruses. While oncolytic viruses show clinical promise in already immunogenic malignancies, response rates are inconsistent. Response rates are even less consistent in immunosuppressed tumor microenvironments like those found in liver, pancreas, and MSI-stable colon cancers. Therefore, the efficacy of oncolytic viruses needs to be improved for more oncolytic viruses to enter mainstream cancer therapy. One approach to increase the therapeutic efficacy of oncolytic viruses is to use them as primers for other immunotherapeutics. The amenability of oncolytic viruses to transgene-arming provides an immense opportunity for investigators to explore different ways of improving the outcome of oncolytic therapy. In this regard, genes encoding immunomodulatory proteins are the most commonly studied genes for arming oncolytic viruses. Other transgenes used to arm oncolytic viruses include those with the potential to favorably modulate tumor stroma, making it possible to image the virus distribution and increase its suitability for combination with other therapeutics. This review will detail the progress made in arming oncolytic viruses with a focus on immune-modulatory transgenes, and will discuss the challenges that need to be addressed for more armed oncolytic viruses to find widespread clinical use.
在过去二十年中，溶瘤病毒疗法领域取得了显著进展，首个溶瘤免疫病毒疗法Talimogene Laherparepvec被批准用于治疗黑色素瘤。大量临床前和临床研究表明其他溶瘤病毒具有良好的安全性。虽然溶瘤病毒在已经具有免疫原性的恶性肿瘤中显示出临床前景，但反应率并不一致。在免疫抑制的肿瘤微环境中，如在肝癌、胰腺癌和微卫星稳定型结肠癌中发现的反应率甚至更不一致。因此，需要提高溶瘤病毒的疗效，以便更多的溶瘤病毒进入主流癌症治疗。提高溶瘤病毒治疗效果的一种方法是将它们用作其他免疫疗法的启动剂。溶瘤病毒对转基因武装的适应性为研究人员探索改善溶瘤治疗结果的不同方法提供了巨大机会。在这方面，编码免疫调节蛋白的基因是武装溶瘤病毒最常研究的基因。用于武装溶瘤病毒的其他转基因包括那些有可能有利地调节肿瘤基质的基因，这使得能够对病毒分布进行成像并提高其与其他疗法联合使用的适用性。本综述将详细介绍在武装溶瘤病毒方面取得的进展，重点是免疫调节转基因，并将讨论为使更多武装溶瘤病毒获得广泛临床应用需要解决的挑战。
