HSV-TK GENE-THERAPY IN HEAD AND NECK SQUAMOUS-CELL CARCINOMA - ENHANCEMENT BY THE LOCAL AND DISTANT BYSTANDER EFFECT

Objective: To determine whether the bystander effect demonstrated in v itro for ganciclovir-mediated killing of a herpes simplex virus thymid ine kinase (HSV-tk) gene-infected human squamous cell carcinoma is ope rative in vivo in a nude mouse model. Design: Prospective study in a m urine model. Intervention: Human head and neck squamous cell carcinoma tumors were grown as xenografts on the flanks or 20 nude mice The tum ors in the left flank were then infected with the HSV-tk gene. Then, a fter 48 hours, the animals were treated with intraperitoneal ganciclov ir twice daily. Assessment of the turners on both flanks was performed over a 31-day period. Main Outcome Measures: Resolution of tumors inf ected with HSV-th gene in animals treated with ganciclovir; resolution of tumors uninfected with HSV-tk gene on the contralateral flank in a nimals created with ganciclovir. Results: Following HSV-th gene therap y in nude mice, complete resolution of HSV-tk-gene-infected human head and neck squamous cell carcinoma tumors was observed following gancic lovir treatment. Uninfected tumors were also noted to regress, but not completely resolve, in response to intraperitoneal ganciclovir (dista nt bystander effect). Conclusion: This study confirms that the local a nd distant bystander effects exist in this murine model, enhancing the possibility of its role for treatment of human squamous cell carcinom a of the head and neck.