Abstract
Purpose: Oncolytic virus (OV) therapy has emerged as a novel tool in our therapeutic arsenals for fighting cancer. As a live biological agent, oncolytic virus has the ability to target and selectively amplify at the tumor sites. We have reported that a vaccinia-based OV (Pexa-Vec) has shown good efficacy in pre-clinical models and in clinical trials. In order to give an additional tool to clinicians to allow both treatment of the tumor and improved visualization of tumor margins, we developed new viral based platforms with two specific gene reporters. Methods: We have incorporated the human sodium iodide symporter (hNIS) and the human somatostatin receptor 2 (hSR) in the vaccinia-based OV and tested viral constructs for their abilities to track and treat tumor development in vivo. Results: Early and high level expression of hNIS is detrimental to the recombinant virus, leading to the aggregation of hNIS protein and early cell death. Putting hNIS under a late synthetic promoter allows a higher functional expression of the protein and much stronger 123I or 99Tc uptake. In vivo, the hNIS-containing virus infects and amplifies in the tumor site, showing a better efficacy than the parental virus. The hNIS expression at the tumor site allows for the imaging of viral infection and tumor regression. Similarly, hSR-containing OV vaccinia infects and lyses cancer cells. Conclusion: When tumor-bearing mice were given hNIS- and hSR-containing OV, radio-isotopes of 99Tc and 111In signals coalesce at the tumor, highlighting the power of using these viruses for tumor diagnosis and treatment.
- Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.