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Combination of mutated herpes simplex virus type 1 (G207 virus) with radiation for the treatment of squamous cell carcinoma of the head and neck

 Se-Heon Kim  ;  Richard J. Wong  ;  David A. Kooby  ;  John F. Carew  ;  Prasad S. Adusumilli  ;  Snehal G. Patel  ;  Jatin P. Shah  ;  Yuman Fong 
 EUROPEAN JOURNAL OF CANCER, Vol.41(2) : 313-322, 2005 
Journal Title
Issue Date
Animals ; Carcinoma, Squamous Cell/radiotherapy ; Carcinoma, Squamous Cell/therapy* ; Cell Line, Tumor ; Combined Modality Therapy/methods ; Genetic Therapy/methods* ; Head and Neck Neoplasms/radiotherapy ; Head and Neck Neoplasms/therapy* ; Herpesvirus 1, Human/genetics* ; Male ; Mice ; Mice, Inbred C3H ; Mutation/genetics* ; Neoplasm Transplantation ; Transplantation, Heterologous ; Virus Replication/genetics* ; Virus Replication/radiation effects
Gene therapyHerpes simplex virusRadiationHead and neck neoplasm
G207 is an oncolytic herpes simplex virus (HSV) with deletions at both γ134.5 loci and a LacZ gene insertion inactivating the HSV ribonucleotide reductase gene. Ionising radiation induces the growth arrest-inducible gene, GADD34, and ribonucleotide reductase. GADD34 is a protein that correlates with apoptosis following radiation and has homology with the G207 γ134.5 gene. We hypothesised that the combination of radiotherapy with G207 may have a potentiating effect on viral replication and anti-tumour efficacy. The purpose of this study was therefore to evaluate the combination of G207 with radiation therapy to treat head and neck tumours. The cytotoxicity of G207 was tested in six head and neck squamous carcinoma cell lines, in the presence or absence of irradiation. For in vivo experiments, flank tumours in C3H/HeJ mice or in nude mice were treated with direct injections of G207, with or without radiation. All head and neck squamous cancer cell lines tested demonstrated significantly increased antitumour effects with the combination of G207 virus and radiation therapy compared with each individual modality (P < 0.01). Furthermore, the combination treatment effect was better than the expected additive effect of the two therapies in combination. Even the radiation-resistant cell lines (SCC25, MSKQLL2, SCCVII) were susceptible. The combination of direct G207 injection with radiation therapy suppressed human and murine squamous cell carcinoma growth significantly (P < 0.05 and P < 0.001) compared with controls or single modality therapy. G207 enhanced the effectiveness of radiation therapy and low-dose radiation potentiated the effectiveness of G207 viral therapy in head and neck cancer. These findings suggest a potential clinical application for this combined therapy as treatment for radiation-resistant head and neck cancers.
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1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Heon(김세헌)
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