Effects of innate immunity on herpes simplex virus and its ability to kill tumor cells
Effects of innate immunity on herpes simplex virus and its ability to kill tumor cells
复制标题
DOI：
10.1038/sj.gt.3302038
复制
发表时间：
2003-06
期刊：
影响因子：
5.1
通讯作者：
H. Wakimoto;P. Johnson;D. Knipe;E. Chiocca
中科院分区：
文献类型：
--
作者：
H. Wakimoto;P. Johnson;D. Knipe;E. Chiocca
已经或正在进行几项临床试验，以测试不同溶瘤病毒株（OV）对恶性肿瘤的安全性和有效性。OV代表在肿瘤细胞中表现出相对选择性复制的天然存在的或遗传工程改造的病毒株。已经从单纯疱疹病毒1（HSV 1）衍生出几种类型的OV。肿瘤的溶瘤作用依赖于OV初始感染肿瘤，随后OV在肿瘤自身内的随后传播的过程。免疫反应在这些过程中的作用尚未得到广泛研究。相反，免疫应答对野生型HSV 1感染和在中枢神经系统中传播的过程的影响已经被详细研究和描述。天然和免疫个体中针对野生型HSV 1感染的第一道防线由先天性体液（补体、细胞因子、趋化因子）和细胞（巨噬细胞、嗜中性粒细胞、NK细胞、γδ T细胞和干扰素产生细胞）应答提供。这些协调病毒粒子和病毒感染细胞的裂解，以及提供有效的适应性免疫的联系。先天防御在减少基因工程HSV的溶瘤作用中的作用最近才被研究，但几种相同的宿主反应似乎在限制复制病毒的抗癌作用中起作用。这些知识的重要性在于找到调节这种初始先天反应的途径，以便在最小化宿主毒性的同时增加肿瘤的溶瘤作用。
Several clinical trials have or are being performed testing the safety and efficacy of different strains of oncolytic viruses (OV) for malignant cancers. OVs represent either naturally occurring or genetically engineered strains of viruses that exhibit relatively selective replication in tumor cells. Several types of OV have been derived from herpes simplex virus 1 (HSV1). Tumor oncolysis depends on the processes of initial OV infection of tumor, followed by subsequent propagation of OV within the tumor itself. The role of the immune responses in these processes has not been extensively studied. On the contrary, effects of the immune response on the processes of wild-type HSV1 infection and propagation in the central nervous system have been studied and described in detail. The first line of defense against a wild-type HSV1 infection in both naive and immunized individuals is provided by innate humoral (complement, cytokines, chemokines) and cellular (macrophages, neutrophils, NK cells, γδ T cells, and interferon-producing cells) responses. These orchestrate the lysis of virions and virus-infected cells as well as provide a link to effective adaptive immunity. The role of innate defenses in curtailing the oncolytic effect of genetically engineered HSV has only recently been studied, but several of the same host responses appear to be operative in limiting anticancer effects by the replicating virus. The importance of this knowledge lies in finding avenues to modulate such initial innate responses, in order to allow for increased oncolysis of tumors while minimizing host toxicity.