Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Surgery. 2013 Sep;154(3):486-95. doi: 10.1016/j.surg.2013.06.004. Epub 2013 Jul 23.
The purpose of this work was to examine the ability of an oncolytic vaccinia virus expressing the human sodium iodine transporter (hNIS) to provide real time monitoring of viral therapy and effective treatment of malignant pleural mesothelioma (MPM).
Infectivity and cytotoxic effects of GLV-1h153 on mesothelioma cell lines of all histologic subtypes were assayed in vitro. Viral replication was examined by standard viral plaque assay. Orthotopic MPM xenografts were generated in athymic nude mice, treated with intrapleural GLV-1h153, and assessed for effect on tumor burden and survival. Orthotopic tumors were also imaged on single photon emission computed tomography (SPECT)/computed tomography (CT) after (131)I administration.
GLV-1h153-infected and killed all cell lines in a time- and concentration-dependent manner. Viral replication demonstrated a >2.5-log increase in titer over 4 days. Intrapleural treatment of orthotopic MPM xenografts resulted in a significant decrease in tumor burden 1 week after treatment and an improvement in survival. Infection of orthotopic xenografts was both therapeutic and facilitated monitoring by (131)I-SPECT/CT via expression of hNIS in infected tissue.
Our results suggest that GLV-1h153 may be a promising therapeutic agent for MPM and warrants further investigation.
本研究旨在评估表达人碘钠同向转运体（hNIS）的溶瘤痘苗病毒在实时监测病毒治疗和有效治疗恶性胸膜间皮瘤（MPM）方面的作用。
体外检测 GLV-1h153 对各种组织学亚型的间皮瘤细胞系的感染性和细胞毒性作用。通过标准病毒空斑分析检测病毒复制。在裸鼠中建立原位 MPM 异种移植瘤模型，给予 GLV-1h153 腔内治疗，并评估对肿瘤负荷和生存的影响。在给予放射性碘（131I）后，通过单光子发射计算机断层扫描（SPECT）/计算机断层扫描（CT）对原位肿瘤进行成像。
GLV-1h153 以时间和浓度依赖的方式感染和杀死所有细胞系。病毒复制在 4 天内增加了 >2.5 个对数。原位 MPM 异种移植瘤的腔内治疗在治疗后 1 周可显著降低肿瘤负荷，并提高生存率。感染原位异种移植瘤不仅具有治疗作用，而且通过感染组织中 hNIS 的表达，方便了放射性碘（131I）-SPECT/CT 的监测。
我们的研究结果表明，GLV-1h153 可能是一种有前途的 MPM 治疗药物，值得进一步研究。
