A novel oncolytic viral therapy and imaging technique for gastric cancer using a genetically engineered vaccinia virus carrying the human sodium iodide symporter

Abstract

BackgroundGastric cancers have poor overall survival despite recent advancements in early detection methods, endoscopic resection techniques, and chemotherapy treatments. Vaccinia viral therapy has had promising therapeutic potential for various cancers and has a great safety profile. We investigated the therapeutic efficacy of a novel genetically-engineered vaccinia virus carrying the human sodium iodide symporter (hNIS) gene, GLV-1 h153, on gastric cancers and its potential utility for imaging with 99mTc pertechnetate scintigraphy and 124I positron emission tomography (PET).MethodsGLV-1 h153 was tested against five human gastric cancer cell lines using cytotoxicity and standard viral plaque assays. In vivo, subcutaneous flank tumors were generated in nude mice with human gastric cancer cells, MKN-74. Tumors were subsequently injected with either GLV-1 h153 or PBS and followed for tumor growth. 99mTc pertechnetate scintigraphy and 124I microPET imaging were performed.ResultsGFP expression, a surrogate for viral infectivity, confirmed viral infection by 24 hours. At a multiplicity of infection (MOI) of 1, GLV-1 h153 achieved > 90% cytotoxicity in MNK-74, OCUM-2MD3, and AGS over 9 days, and >70% cytotoxicity in MNK- 45 and TMK-1. In vivo, GLV-1 h153 was effective in treating xenografts (p < 0.001) after 2 weeks of treatment. GLV-1 h153-infected tumors were readily imaged by 99mTc pertechnetate scintigraphy and 124I microPET imaging 2 days after treatment.ConclusionsGLV-1 h153 is an effective oncolytic virus expressing the hNIS protein that can efficiently regress gastric tumors and allow deep-tissue imaging. These data encourages its continued investigation in clinical settings.

TGFβ3-mediated induction of Periostin facilitates head and neck cancer growth and is associated with metastasis

“…Apart from the transforming growth factor-beta-induced protein (TGFBI) which is a secreted ECM component that can play an important role in tumor progression 25 26 , POSTN, parathyroid hormone-like hormone (PTHLH) and secreted phosphoprotein 1 (SPP1) were also predicted to be associated with skeletal system development. Our research group have previously reported that PTHLH can act as a tumor promoter, affecting cell proliferation and the cell cycle in HNC 27 . Thereafter, the expression levels of POSTN and SPP1 were tested in 29 paired HNC samples through real-time PCR.…”

The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications

“…Its oncolytic activity has been documented in several in vitro and in vivo studies. VV carrying the human NIS gene has been investigated as a possible treatment for endometrial cancer (144), pancreatic cancer (145, 146), malignant pleural mesothelioma (147), and gastric cancer (148) by in vitro and in vivo monitoring of infection, distribution, and cytotoxicity. Tumor growth and reduction were measured by 99m TcO 4 − and 124 I − SPECT/CT.…”

The Evolution of Poxvirus Vaccines

“…As we have described for infectious diseases, in the development of different vaccines against cancer, various approaches involve the insertion of heterologous genes into common poxvirus strains, such as immunotherapy by the expression of TAA (e.g., MUC1 [578], oncofetal antigen 5T4 [579], PSA [580], CEA [581]), the expression of immunomodulatory genes (e.g., costimulatory molecules-B7.1, B7.2 [582], CD80 [583] or cytokines-IL-2 [584], IFN-β [585], GM-CSF [586]), the expression of suicide genes (e.g., cytosine deaminase [587], purine nucleoside phosphorylase [588]), and the expression of genes used for the imaging as a support for combination therapies (thyroidal sodium iodide symporter NIS [589]).…”