Combination of Mutated Herpes Simplex Virus (G207) with Radiation for the Treatment of Squamous Cell Carcinoma of the Head and Neck

Kim, Se Heon; Choi, Eun Chang; Han, Dong Hee; Han, Su Jin; Kim, Jeong Hong; Nam, Jee In; Kim, Kwang Moon

Abstract

BACKGROUND AND OBJECTIVES
G207 virus is an ideal candidate of oncolytic viral therapy. It is a multi-gene mutant of HSV-1 with a deletion at the gamma34.5 loci and a LacZ gene insertion in the ICP6 gene, encoding the HSV ribonucleotide reductase. Ionizing radiation induces the growth arrest-inducible gene, Gadd34, a protein that correlates with apoptosis following radiation and has homology with the G207 gamma34.5 gene. It is hypothesized that the combination of radiotherapy with G207 virus may have a synergic effect on viral replication and efficacy. The purpose of this study is to evaluate the combination of the cytotoxic G207 virus with radiation therapy to treat head and neck tumors. MATERIALS AND METHOD: Five human SCCHN cell lines and one murine SCC cell line were utilized in this study. There were two groups of cells: control cells received no irradiation while the second group was irradiated with 400 cGy. Cells were infected with G207 vectors at a multiplicity of infection (MOI) of 0.1. Cytotoxicity assay was performed for 5 days. Cells and culture medium supernatant were collected and viral titers determined by plaque forming units on Vero cells. To evaluate infection efficiency, X-gal staining was performed at 24hr post infection. RESULTS: All head and neck squamous cancer cell lines tested demonstrated an increased susceptibility to the combination of G207 virus with radiation therapy when compared with each single modality (more than additive effect, p<0.05). Even though cell lines such as SCC25, MSKQLL2, or SCCVII were radioresistant, the combination of G207 with radiation therapy showed significantly increased cytotoxic effect. X-gal staining and viral growth curve studies demonstrated that G207 replications in radiated cell lines were not decreased as compared with non-radiated ones. CONCLUSION: The results provide preliminary support for the use of G207 oncolytic virus as a radiation adjuvant in treatment of head and neck cancer. The combination of radiation and oncolytic viral gene therapy may eventually be useful in treating patients with radio-resistant, non-resectable disease, and patients with a high probability of contracting postoperative microscopic residual diseases.