Purpose Gene-directed enzyme prodrug therapy (GDEPT)
is a ‘‘Trojan-horses’’ suicide gene therapy that consists of
tumor-targeted gene delivery (vectorized by mesenchymal
stem cells MSCs) encoding an enzyme that converts a
harmless prodrug into cytotoxic metabolites in situ. Then,
cytotoxic metabolites passively diffuse in the neighboring
tumor cells and kill them (bystander effect). The goal of
our study was to assess the feasibility and efficacy of intra-
arterial administration of MSCs transduced with an opti-
mized gene (MSC-CYP2B6TM-RED) followed by intra-
venous administration of cyclophosphamide (CPA) into the
VX2 rabbit liver tumor.
Materials and Methods Nine rabbits with a VX2 liver
tumor were randomly assigned into three groups: Control
group A (one rabbit) free of any treatment; Control group B
(two rabbits) receiving intravenous injection of
cyclophosphamide at day 3 and CPA at day 14; and Group
C (six rabbits) receiving the GDEPT treatment, consisting