Gene therapy is an attractive approach for
hepatocellular carcinoma (HCC) patients. Nevertheless, efficient transgene delivery remains a challenge. In this study, we explored a new targeted system based on human umbilical cord-derived mesenchymal stem cells (HUMSCs), which were engineered to deliver adenovirus to
tumor sites, and to replicate and assemble into new adenovirus against HCC. Our results showed that HUMSCs infected by Ad-hTERTp-IL24 followed by LentiR.E1A
infection could specifically migrate to HepG2
tumor cells and support adenoviral replication in vitro and in vivo 36 h after LentiR.E1A
infection. Ad-hTERTp-IL24 specifically inhibited HepG2 cells growth, and this inhibitory effect was enhanced by low doses of
5-fluorouracil (5-Fu), because the expression levels of
coxsackie adenovirus receptor (CAR) and
integrin ανβ3 on
tumor cells were significantly increased, causing higher viral uptake. Compared with the no treatment groups, Ad-hTERTp-IL24 and LentiR.E1A co-loaded HUMSCs exhibited significant anti-
tumor activity in vivo, particularly in combination with low doses of
5-Fu. In summary, this study provides a promising targeted gene therapeutic strategy dependent on the
tumor tropism of HUMSCs, to improve the outcome of virotherapy for
tumor patients especially those with metastatic diseases.