EXTH-86. Therapeutic Potential of SHED-Derived Suicide Gene Therapy for Brain Tumors Using HSV-TK/Ganciclovir System

INTRODUCTION Effective treatment of malignant brain tumors remains a significant challenge due to their infiltrative nature and resistance to conventional therapies. Suicide gene therapy using herpes simplex virus thymidine kinase (HSV-TK) in combination with ganciclovir (GCV) has shown promise when delivered via stem cells. Stem cells derived from human exfoliated deciduous teeth (SHED) offer a readily accessible, ethically favorable, and highly migratory cell source. This study investigates the feasibility of SHED engineered to express HSV-TK (SHED-TK) as a novel therapeutic vector against gliomas and metastatic brain tumors. METHODS SHED-TK cells were co-cultured with glioma (U87) or non-small cell lung cancer (NSCLC) lines (H1299, A549, H460) in the presence of GCV to evaluate the bystander cytotoxic effect. SHED-TK migratory behavior was analyzed using Matrigel-based migration assays. For in vivo analysis, tumor-bearing nude mice received SHED-TK injections followed by GCV administration. Tumor growth was monitored via bioluminescence imaging, and overall survival was recorded. RESULTS SHED-TK cells exhibited high GCV sensitivity. In vitro, SHED-TK exerted significant bystander-mediated cytotoxicity across all tumor cell lines. In vivo, SHED-TK combined with GCV led to marked tumor suppression and significantly prolonged survival compared to controls. Bioluminescence remained stable only in the SHED-TK+GCV group, while tumors progressed in all other groups. SHED-TK cells implanted contralaterally migrated effectively through the corpus callosum to reach tumor sites. CONCLUSION SHED-TK cells demonstrated robust tumor-tropic migration and potent antitumor efficacy via the HSV-TK/GCV system. These findings support SHED-TK as a promising delivery platform for suicide gene therapy in primary and metastatic brain tumors. Ongoing studies aim to enhance therapeutic outcomes through combination strategies with oncolytic virotherapy.