Hypopharyngeal
carcinoma is one of the most aggressive subtypes of
squamous cell carcinoma of the head and neck. Although significant progress has been made in surgical techniques,
radiotherapy, and
chemotherapy, the prognosis is still poor. Mesenchymal stem cells (MSCs) have attracted substantial attention as
tumor-targeted cellular carriers for cancer gene
therapy. We have previously shown that recombinant baculovirus-adeno-associated vectors (BV-AAV) possessed high efficiency for multi-gene coexpression in human bone marrow MSCs (BMSCs) and BV-AAV-engineered BMSCs could effectively target
hypopharyngeal cancer tissues in vivo. However, it was not clear whether BV-AAV-engineered BMSCs as cellular vehicles, mediating the expression of the
sodium iodide symporter (NIS), would be effective in controlling the growth of hypopharyngeal
carcinoma by radioiodine
therapy. We constructed a hybrid BV-AAV containing the Luc-P2A-eGFP fusion or NIS sequence to modify BMSCs (BMSCs-Bac-Luc-P2A-eGFP or BMSCs-Bac-NIS). The 125I uptake of BMSCs-Bac-NIS was analyzed by an automatic gamma counter in vitro and micro-single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging in vivo. The value of radioiodine
therapy for hypopharyngeal
carcinoma was evaluated by measuring
tumor volume,
glucose metabolism (via 2-deoxy-2-[18F]
glucose [18F-FDG] positron emission tomography/CT), and proliferation of
tumor cells. We demonstrated that 125I uptake of BMSCs-Bac-NIS persists over long-term in vitro (at least 8 h). Radioactive uptake could be detected by SPECT/CT 1 h after 125I injection in the BMSCs-Bac-NIS group, showing that this strategy allows for the tracking of real-time migration and transgene expression of BMSCs. Radioiodine
therapy resulted in a significant reduction in
tumor growth (386.93 ± 249.23 mm3 vs 816.56 ± 213.87 mm3 in controls), increased survival, and decreased SUVmax of
18F-FDG. The hybrid BV-AAV that can provide a variety of genes and regulatory elements, as a novel gene therapy strategy opens the prospect of NIS-mediated
radionuclide therapy of hypopharyngeal
carcinoma after MSC-mediated gene delivery.