Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
Cancer Gene Ther. 2013 May;20(5):282-9. doi: 10.1038/cgt.2013.18. Epub 2013 Apr 26.
Oncolytic viruses are attractive cancer therapeutics because of their unique mechanisms of tumor cell targeting and the absence of toxic side effects associated with current treatments. Bovine herpesvirus type 1 (BHV-1) is a species-specific herpesvirus that fails to induce cytopathic effects in normal human cells, but is capable of infecting and killing a variety of immortalized and transformed human cell types, including human breast tumor cell lines from luminal, basal A and basal B subtypes, representing a variety of receptor expression profiles. BHV-1 is capable of initiating replication in and killing both bulk and side population cells, the latter of which have enhanced tumor-initiating capacity. Despite the lack of a productive infection or secretion of cytotoxic factors, BHV-1 infection decreases cellular viability in long-term culture following low multiplicity of infection. Moreover, BHV-1-infected MCF7 cells are significantly diminished in their capacity to form tumors in vivo. Overall, these studies suggest that oncolytic BHV-1 targets bulk breast cancer cells and cancer-initiating cells from luminal and basal subtypes by a novel mechanism that is not contingent upon cellular receptor expression status.
溶瘤病毒因其独特的肿瘤细胞靶向机制和当前治疗方法中不存在的毒性副作用而成为有吸引力的癌症治疗方法。牛疱疹病毒 1 型（BHV-1）是一种种特异性疱疹病毒，不能在正常的人类细胞中诱导细胞病变效应，但能够感染和杀死多种永生化和转化的人类细胞类型，包括腔、基底 A 和基底 B 亚型的人类乳腺癌细胞系，代表了多种受体表达谱。BHV-1 能够在批量和侧群细胞中启动复制并杀死这些细胞，后者具有增强的肿瘤起始能力。尽管缺乏有效的感染或细胞毒性因子的分泌，BHV-1 感染仍会在低感染复数的长期培养中降低细胞活力。此外，BHV-1 感染的 MCF7 细胞在体内形成肿瘤的能力显著降低。总的来说，这些研究表明，溶瘤性 BHV-1 通过一种新型机制靶向腔性和基底亚型的乳腺癌细胞和起始肿瘤细胞，而这种机制不依赖于细胞受体表达状态。
