HSV-tk Gene Therapy in Head and Neck Squamous Cell Carcinoma: Enhancement by the Local and Distant Bystander Effect

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Abstract
Objective: To determine whether the bystander effect demonstrated in vitro for ganciclovir-mediated killing of a herpes simplex virus thymidine kinase (HSV-tk) geneinfected human squamous cell carcinoma is operative in vivo in a nude mouse model. Design: Prospective study in a murine model. Intervention: Human head and neck squamous cell carcinoma tumors were grown as xenografts on the flanks of 20 nude mice. The tumors in the left flank were then infected with the HSV-tk gene. Then, after 48 hours, the animals were treated with intraperitoneal ganciclovir twice daily. Assessment of the tumors on both flanks was performed over a 31-day period. Main Outcome Measures: Resolution of tumors infected with HSV-tk gene in animals treated with ganciclovir; resolution of tumors uninfected with HSV-tk gene on the contralateral flank in animals treated with ganciclovir. Results: Following HSV-tk gene therapy in nude mice, complete resolution of HSV-tk- gene-infected human head and neck squamous cell carcinoma tumors was observed following ganciclovir treatment. Uninfected tumors were also noted to regress, but not completely resolve, in response to intraperitoneal ganciclovir (distant bystander effect). Conclusion: This study confirms that the local and distant bystander effects exist in this murine model, enhancing the possibility of its role for treatment of human squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. 1996;122:746-749