Anti-tumour activity of oncolytic reovirus against canine histiocytic sarcoma cells
Anti-tumour activity of oncolytic reovirus against canine histiocytic sarcoma cells
复制标题
DOI：
10.1111/vco.12468
复制
发表时间：
2019-06-01
影响因子：
2.1
通讯作者：
Mizuno, Takuya
中科院分区：
文献类型：
--
作者：
Igase, Masaya;Shousu, Kazuha;Mizuno, Takuya
犬组织细胞肉瘤是一种侵袭性、致死性的肿瘤性疾病，预后不良。洛莫司汀通常被接受为一线全身治疗，尽管该化合物不能提供完全消退。因此，需要研究一种新的方法来治疗犬组织细胞肉瘤。然而，使用呼肠孤病毒对组织细胞肉瘤进行溶瘤治疗的抗肿瘤作用尚不清楚。在这里，我们发现呼肠孤病毒在犬组织细胞肉瘤细胞系中具有体外和体内溶瘤活性。我们发现呼肠孤病毒可以在犬组织细胞肉瘤细胞系中复制并诱导半胱天冬酶依赖的凋亡。单次瘤内注射呼肠孤病毒完全抑制了NOD/SCID小鼠皮下移植肿瘤的生长。此外，我们证明，呼肠孤病毒诱导的细胞死亡的易感性是由于在体外呼肠孤病毒感染诱导的I型干扰素的表达程度。总之，溶瘤呼肠孤病毒似乎是组织细胞肉瘤的有效治疗选择，因此需要在早期临床试验中进一步研究。
Canine histiocytic sarcoma is an aggressive, fatal neoplastic disease with a poor prognosis. Lomustine is generally accepted as the first-line systemic therapy, although this compound does not provide complete regression. Therefore, research into a novel approach against canine histiocytic sarcoma is needed. However, anti-tumour effects of oncolytic therapy using reovirus against histiocytic sarcoma are unknown. Here, we showed that reovirus has oncolytic activity in canine histiocytic sarcoma cell lines in vitro and in vivo. We found that reovirus can replicate and induce caspase-dependent apoptosis in canine histiocytic sarcoma cell lines. A single intra-tumoural injection of reovirus completely suppressed the growth of subcutaneously grafted tumours in NOD/SCID mice. Additionally, we demonstrated that susceptibility to reovirus-induced cell death was attributable to the extent of expression of type I interferons induced by reovirus infection in vitro. In conclusion, oncolytic reovirus appears to be an effective treatment option for histiocytic sarcoma, and therefore warrants further investigation in early clinical trials.