Li Hongtao, Zhang Xiaoliu
Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
Methods Mol Biol. 2010;651:279-90. doi: 10.1007/978-1-60761-786-0_16.
It is well documented that immunotherapy has a great potential for cancer treatment. The ideal cancer immunotherapeutic strategies should be relatively simple, but able to trick the host's immune system to elicit a robust immune response to the tumor target. Herpes Simplex Virus (HSV) has been engineered for the purpose of oncolysis. These so-called oncolytic HSVs can selectively replicate within tumor cells, resulting in their destruction and in the production of progeny virions that can spread to adjacent tumor cells. In addition to their direct oncolytic effect, tumor lysis by oncolytic viruses releases tumor antigens in their native form and configuration in an individualized way. Immune responses thus generated would be more likely to recognize the original tumor than would tumor vaccines produced by other methods, most of which require extensive in vitro modification and manipulation. Several recently published studies have shown that HSV-elicited antitumor immune responses are an essential part of the overall antitumor effect produced by oncolytic HSVs, not only for controlling primary tumor growth, but also for preventing long distance metastases. In this chapter several key methods will be illustrated to monitor the immune response elicited by oncolytic HSVs.
有充分文献记载,免疫疗法在癌症治疗方面具有巨大潜力。理想的癌症免疫治疗策略应相对简单,但能够诱使宿主免疫系统对肿瘤靶点引发强烈的免疫反应。单纯疱疹病毒(HSV)已被改造用于溶瘤目的。这些所谓的溶瘤性HSV能够在肿瘤细胞内选择性复制,导致肿瘤细胞破坏,并产生可扩散至邻近肿瘤细胞的子代病毒粒子。除了直接的溶瘤作用外,溶瘤病毒引起的肿瘤溶解以个体化方式释放天然形式和构型的肿瘤抗原。如此产生的免疫反应比其他方法生产的肿瘤疫苗更有可能识别原始肿瘤,其他方法大多需要广泛的体外修饰和操作。最近发表的几项研究表明,HSV引发的抗肿瘤免疫反应是溶瘤性HSV产生的总体抗肿瘤效应的重要组成部分,不仅用于控制原发性肿瘤生长,还用于预防远距离转移。在本章中,将阐述几种监测溶瘤性HSV引发的免疫反应的关键方法。