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

Gholami, Sepideh, Haddad, Dana, Chen, Chun-Hao, Chen, Nanhai G, Zhang, Qian, Zanzonico, Pat B, Szalay, Aladar A, Fong, Yuman (December 2011) Novel therapy for anaplastic thyroid carcinoma cells using an oncolytic vaccinia virus carrying the human sodium iodide symporter. Surgery, 150 (6). pp. 1040-1047. ISSN 0039-6060

URL: https://www.ncbi.nlm.nih.gov/pubmed/22136819
DOI: 10.1016/j.surg.2011.09.010

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.

Item Type: Paper
Subjects: diseases & disorders > cancer
therapies > viral vectors
CSHL Authors:
Communities: CSHL labs > Gholami Lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: December 2011
Date Deposited: 05 Oct 2023 20:27
Last Modified: 05 Oct 2023 20:27
Related URLs:
URI: https://repository.cshl.edu/id/eprint/41166

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