Hepatic Intra-arterial Delivery of a “Trojan-horses” Gene Therapy: A Pilot Study on Rabbit VX2 Hepatic Tumor Model

摘要: Gene-directed enzyme prodrug therapy (GDEPT) is a “Trojan-horses” suicide gene that consists of tumor-targeted delivery (vectorized by mesenchymal stem cells MSCs) encoding an converts harmless into cytotoxic metabolites in situ. Then, passively diffuse the neighboring tumor and kill them (bystander effect). The goal our study was to assess feasibility efficacy intra-arterial administration MSCs transduced with optimized (MSC-CYP2B6TM-RED) followed intravenous cyclophosphamide (CPA) VX2 rabbit liver tumor. Nine rabbits were randomly assigned three groups: Control group A (one rabbit) free any treatment; B (two rabbits) receiving injection at day 3 CPA 14; Group C (six GDEPT treatment, consisting successive transduced-MSCs days 0 (n = 6) 11 (n = 3), 14 (n = 3). response assessed ultrasound scan every 7 days histopathological analysis sacrifice (D25). There significant difference volume between control groups (A + B) D7: 38/19 cm3 (p = 0.024); D11: 51/20 cm3 (p = 0.024), D25: 121/37 cm3 (p = 0.048). Tumor necrosis significantly greater metastatic spread lower for who received (78% total surface) than animals (22% surface (p = 0.006). Intra-arterial feasible and, after injection, resulted 78% (p = 0.006) less metastasis model.