Factors that limit the effectiveness of herpes simplex virus type 1 for treatment of oral cancer in mice.
Factors that limit the effectiveness of herpes simplex virus type 1 for treatment of oral cancer in mice.
复制标题
限制 1 型单纯疱疹病毒治疗小鼠口腔癌有效性的因素。
DOI：
10.1158/1078-0432.ccr-04-2302
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Pellenz,Christopher
中科院分区：
文献类型：
--
作者：
Shillitoe,EdwardJ;Pellenz,Christopher
虽然感染1型单纯疱疹病毒（HSV-1）可以抑制实验性口腔癌的生长，但效果是不完全的。为了确定可能限制病毒有效性的因素，我们检查了先天免疫系统的作用和肿瘤细胞的复制状态。AT-84肿瘤在具有特异性免疫缺陷的小鼠品系中被诱导，并被病毒治疗。移植的肿瘤和培养的肿瘤细胞也被感染。在缺乏T淋巴细胞或B淋巴细胞、自然杀伤细胞、吞噬性脾细胞或补体的小鼠之间，病毒复制或病毒对肿瘤的影响没有差异。在作为外植体保存的肿瘤中，病毒的复制并没有明显增加。从肿瘤中恢复细胞后，S期细胞的比例约为18%，病毒在这些细胞中的复制非常有限。培养3周后，S中的比例增加到50%，细胞中病毒的回收率和病毒对细胞的毒性作用都明显增加。因此，当将先天免疫系统作为一种溶瘤病毒用于治疗小鼠口腔癌时，它对HSV-1复制的影响似乎微乎其微。相反，处于S期的细胞比例是重要的。由于人类口腔癌和小鼠肿瘤一样，处于S期的细胞比例很低，因此它们的HSV-1病毒作为癌症治疗可能会受到病毒复制的限制。
Although the growth of experimental oral cancers can be inhibited by infection with the herpes simplex virus type 1 (HSV-1), the effect is incomplete. To define factors that might limit the effectiveness of the virus, we examined the roles of the innate immune system and the replication status of the tumor cells. AT-84 tumors were induced in strains of mice that had specific immune defects and were treated with the virus. Explanted tumors and tumor cells in culture were also infected. No differences in viral replication or in the effect of virus on the tumor were seen between mice with a lack of T or B lymphocytes, natural killer cells, phagocytic spleen cells, or complement. The virus did not replicate significantly more in tumors that were maintained as explants. Immediately after recovery of cells from a tumor the proportion of cells in the S phase was around 18%, and replication of virus in those cells was very limited. After 3 weeks in culture, the proportion in S had increased to 50% and both the recovery of virus from the cells and the toxic effect of the virus on the cells had increased significantly.The innate immune system thus seemed to have a minimal effect on replication of HSV-1 when used as an oncolytic virus for oral cancers in mice. Instead, the fraction of cells in the S phase was important. Because human oral cancers, like mouse tumors, have a low fraction of cells in the S phase, it is likely that thein vivouse of HSV-1 as cancer therapy will be limited by the replication of the virus.