利用携带人钠碘转运体的溶瘤痘苗病毒治疗间变性甲状腺癌细胞的新疗法。

Novel therapy for anaplastic thyroid carcinoma cells using an oncolytic vaccinia virus carrying the human sodium iodide symporter.

机构信息

Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

出版信息

Surgery. 2011 Dec;150(6):1040-7. doi: 10.1016/j.surg.2011.09.010.

DOI:10.1016/j.surg.2011.09.010

PMID:22136819

Abstract

BACKGROUND

Anaplastic thyroid carcinoma (ATC) is fatal with resistance to radiotherapy because of the loss of intrinsic human sodium iodine symporter (hNIS). We determined whether vaccinia virus carrying hNIS kills and induces hNIS reexpression in ATC cells, facilitating deep-tissue imaging.

METHODS

Vaccinia virus (GLV-1h153) carrying hNIS was tested against ATC lines for killing and replication via cytotoxicity and viral plaque assays. Cellular radiouptake was determined using radiouptake assays. GLV-1h153-infected ATC xenografts were imaged via (99m)Tc-pertechnetate.

RESULTS

GLV-1h153 infected, replicated in, and killed all ATC cell lines. GFP expression confirmed viral infection by 24 hours. At a multiplicity of infection (MOI) of 1.0, GLV-1h153 reached near 100% cytotoxicity in 8305c and FRO by day 5 and 70% in the least sensitive cell line, 8505c. GLV-1h153-infected ATC cells had a 14-fold increase of hNIS-specific radiouptake compared with uninfected control 24 hours after infection at an MOI of 1.0. In vivo, GLV-1h153 facilitated imaging of hNIS expression in 8505c tumors using (99m)Tc-pertechnetate.

CONCLUSION

GLV-1h153 is an effective oncolytic agent against ATC. The results show hNIS-specific radiouptake in infected ATC cells, facilitating deep-tissue imaging. GLV-1h153 is a promising candidate for treatment and imaging, and potentially enhancing susceptibility to radioiodine therapy by converting non-hNIS-expressing cells into hNIS-expressing ATC cells.

摘要

背景

由于人源钠碘同向转运体（hNIS）的缺失，间变性甲状腺癌（ATC）对放疗具有耐药性，因此导致其致死率极高。我们旨在明确携带 hNIS 的牛痘病毒是否可以杀伤 ATC 细胞并诱导 hNIS 重新表达，从而促进深层组织成像。

方法

通过细胞毒性和病毒斑测定，检测携带 hNIS 的牛痘病毒（GLV-1h153）对 ATC 系的杀伤和复制作用。通过放射性摄取测定评估细胞放射性摄取。通过放射性核素（99m）Tc-高锝酸盐对 GLV-1h153 感染的 ATC 异种移植瘤进行成像。

结果

GLV-1h153 可感染、复制并杀伤所有 ATC 细胞系。24 小时时 GFP 表达证实了病毒感染。在感染复数（MOI）为 1.0 时，GLV-1h153 在 8305c 和 FRO 细胞中于第 5 天达到近 100%的细胞毒性，在最不敏感的细胞系 8505c 中达到 70%。在 MOI 为 1.0 时，感染后 24 小时，与未感染对照相比，GLV-1h153 感染的 ATC 细胞 hNIS 特异性放射性摄取增加了 14 倍。在体内，使用放射性核素（99m）Tc-高锝酸盐，GLV-1h153 促进了 8505c 肿瘤中 hNIS 表达的成像。