Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus.
Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus.
复制标题
DOI：
10.1186/1479-5876-9-36
复制
发表时间：
2011-03-31
影响因子：
7.4
通讯作者：
Szalay AA
中科院分区：
文献类型：
--
作者：
Haddad D;Chen NG;Zhang Q;Chen CH;Yu YA;Gonzalez L;Carpenter SG;Carson J;Au J;Mittra A;Gonen M;Zanzonico PB;Fong Y;Szalay AA
溶瘤病毒有望治疗癌症。然而，为了评估治疗效果和潜在毒性，需要一种无创成像方式。本研究旨在确定插入人碘化钠同调体（hNIS） cDNA作为病毒治疗的无创成像标记是否会改变一种新型牛痘病毒GLV-1h153的复制和溶瘤能力。GLV-1h153是由亲本牛痘病毒GLV-1h68经同源重组修饰而成的携带hNIS病毒。通过病毒斑块实验和流式细胞术检测GLV-1h153对人胰腺癌细胞系PANC-1的复制能力。采用Westernblot和免疫荧光法检测感染细胞中hNIS的表达和转运情况。使用放射性吸收测定法评估细胞内放射性碘的摄取。并测定了经处理的panc -1异种肿瘤裸鼠的病毒细胞毒性和肿瘤消退。最后，通过使用无载流子124I放射性示踪剂的正电子发射断层扫描（PET）评估异种移植物的肿瘤吸收。GLV-1h153与GLV-1h68一样有效地感染、复制并杀死PANC-1细胞。GLV-1h153在感染细胞中提供了剂量依赖性的hNIS表达水平。免疫荧光检测到在细胞裂解之前蛋白质转运到细胞膜，增强了hnis特异性的放射性摄取（P < 0.001）。在体内，GLV-1h153与GLV-1h68在退行性胰腺癌异种移植中的安全性和有效性相同（P < 0.001）。最后，瘤内注射GLV-1h153有助于通过124I-PET成像肿瘤中的病毒复制。插入hNIS基因不会阻碍GLV-1h153的复制或溶瘤能力，使这种新型病毒成为无创成像和溶瘤病毒治疗跟踪的有希望的新候选病毒。
Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide symporter (hNIS) cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153. GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry hNIS via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of hNIS in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenografts was assessed via positron emission tomography (PET) utilizing carrier-free 124I radiotracer. GLV-1h153 infected, replicated within, and killed PANC-1 cells as efficiently as GLV-1h68. GLV-1h153 provided dose-dependent levels of hNIS expression in infected cells. Immunofluorescence detected transport of the protein to the cell membrane prior to cell lysis, enhancing hNIS-specific radiouptake (P < 0.001). In vivo, GLV-1h153 was as safe and effective as GLV-1h68 in regressing pancreatic cancer xenografts (P < 0.001). Finally, intratumoral injection of GLV-1h153 facilitated imaging of virus replication in tumors via 124I-PET. Insertion of the hNIS gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy.
登录
查看更多内容
影响因子：
12.4
作者：
McCart, JA;Mehta, N;Bartlett, DL
通讯作者：
Bartlett, DL
影响因子：
3.8
作者：
Lin, Shu-Fu;Yu, Zhenkun;Wong, Richard J.
通讯作者：
Wong, Richard J.
影响因子：
5.8
作者：
Seissler, J;Wagner, S;Morgenthaler, MG
通讯作者：
Morgenthaler, MG
影响因子：
5.8
作者：
Lin, Shu-Fu;Price, Daniel L.;Wong, Richard J.
通讯作者：
Wong, Richard J.
影响因子：
6.4
作者：
Kelly, Kaitlyn J.;Brader, Peter;Woo, Yanghee;Li, Sen;Chen, Nanhai;Yu, Yong A.;Szalay, Aladar A.;Fong, Yuman
通讯作者：
Fong, Yuman