Stiles Brendon M, Bhargava Amit, Adusumilli Prasad S, Stanziale Stephen F, Kim Teresa H, Rusch Valerie W, Fong Yuman
Department of Surgery, the Hepatobiliary Division and the Thoracic Division, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Surgery. 2003 Aug;134(2):357-64. doi: 10.1067/msy.2003.244.
The oncolytic herpes simplex-1 virus, NV1066, is a replication-competent virus that has been engineered to infect and lyse tumor cells selectively and to carry a transgene for enhanced green fluorescent protein (EGFP). The purpose of this study was to determine viral cytotoxicity in an esophageal cancer cell line and to determine whether EGFP expression could be used as a marker of viral infection.
BE3 esophageal adenocarcinoma cells were infected with NV1066 in vitro to determine cell kill and viral replication. EGFP expression was assessed by flow cytometry. The in vivo anti-tumor activity of NV1066 was tested in subcutaneous and intraperitoneal xenograft models. EGFP expression was localized in vivo by fluorescent microscopy and fluorescent laparoscopy.
NV1066 effectively replicated within and killed BE3 cells in vitro and in vivo. EGFP expression identified infected tumor cells. After NV1066 treatment in vivo, EGFP expression localized to the tumor. In an intraperitoneal tumor model, EGFP could be visualized endoscopically using a laparoscope with a fluorescent filter.
NV1066 has oncolytic activity against the BE3 cell line and may be a useful therapy against esophageal cancer. EGFP expression localizes the virus and may help to identify tumor deposits in vivo. Oncolytic activity with NV1066 against gastrointestinal cancers may potentially be tracked by endoscopy.
溶瘤单纯疱疹病毒1型NV1066是一种具有复制能力的病毒，经改造后可选择性感染并裂解肿瘤细胞，并携带增强型绿色荧光蛋白（EGFP）的转基因。本研究的目的是确定该病毒在食管癌细胞系中的细胞毒性，并确定EGFP表达是否可作为病毒感染的标志物。
体外使用NV1066感染BE3食管腺癌细胞，以确定细胞杀伤和病毒复制情况。通过流式细胞术评估EGFP表达。在皮下和腹腔异种移植模型中测试NV1066的体内抗肿瘤活性。通过荧光显微镜和荧光腹腔镜在体内定位EGFP表达。
NV1066在体外和体内均能在BE3细胞内有效复制并杀伤细胞。EGFP表达可识别受感染的肿瘤细胞。在体内给予NV1066治疗后，EGFP表达定位于肿瘤部位。在腹腔肿瘤模型中，使用带有荧光滤光片的腹腔镜可在内窥镜下观察到EGFP。
NV1066对BE3细胞系具有溶瘤活性，可能是一种有效的食管癌治疗方法。EGFP表达可定位病毒，并可能有助于在体内识别肿瘤沉积物。NV1066对胃肠道癌症的溶瘤活性可能可通过内镜进行追踪。
