Li Hongtao, Dutuor Aurelie, Tao Lihua, Fu Xinping, Zhang Xiaoliu
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Clin Cancer Res. 2007 Jan 1;13(1):316-22. doi: 10.1158/1078-0432.CCR-06-1625.
We recently constructed an oncolytic virus from type 2 herpes simplex virus (HSV-2) that selectively targets and kills tumor cells with an activated Ras signaling pathway. Designated FusOn-H2, this virus has shown several discrete killing mechanisms. Here, we evaluated the antitumor immune responses after FusOn-H2-mediated virotherapy in a syngeneic murine neuroblastoma model.
We directly injected FusOn-H2 into established tumors and then measured its antitumor effect and the accompanying tumor-specific immune responses. Several oncolytic HSVs constructed from HSV-1 were included in the same experiments for comparisons.
Our data show that tumor destruction by FusOn-H2 in vivo induces potent antitumor immune responses in this syngeneic neuroblastoma model. The elicited cellular immunity not only eradicated neuroblastoma cells in vitro but also inhibited the growth of tumors at sites distant from the virus injection site. Moreover, adoptive transfer of splenocytes from mice receiving virotherapy to naïve mice resulted in a measurable antitumor effect.
We conclude that the ability of FusOn-H2 to induce tumor-specific cellular immunity expands the oncolytic repertoire of this virus and increases the likelihood that its use in patients would produce significant therapeutic benefits.
我们最近构建了一种源自2型单纯疱疹病毒（HSV - 2）的溶瘤病毒，它能选择性地靶向并杀死具有激活的Ras信号通路的肿瘤细胞。这种名为FusOn - H2的病毒已显示出多种不同的杀伤机制。在此，我们在同基因小鼠神经母细胞瘤模型中评估了FusOn - H2介导的病毒疗法后的抗肿瘤免疫反应。
我们将FusOn - H2直接注射到已形成的肿瘤中，然后测量其抗肿瘤效果以及伴随的肿瘤特异性免疫反应。由HSV - 1构建的几种溶瘤HSV也包含在相同实验中用于比较。
我们的数据表明，在这个同基因神经母细胞瘤模型中，FusOn - H2在体内对肿瘤的破坏诱导了强大的抗肿瘤免疫反应。引发的细胞免疫不仅在体外根除了神经母细胞瘤细胞，还抑制了远离病毒注射部位的肿瘤生长。此外，将接受病毒疗法的小鼠的脾细胞过继转移到未接触过病毒的小鼠中产生了可测量的抗肿瘤效果。
我们得出结论，FusOn - H2诱导肿瘤特异性细胞免疫的能力扩展了该病毒的溶瘤功能谱，并增加了其用于患者时产生显著治疗益处的可能性。
