Experimental study of baculovirus-mediated transfer of the thyroid sodium/iodide symporter gene into thyroid cancer for targeted radiotherapy

Objective: To explore the radiotherapy of thyroid cancers by delivering the sodium/iodide symporter (NIS) gene into the tumor cells using baculoviral vector. Methods: The recombinant baculovirus encoded human NIS gene (BacNIS) was constructed under the control of the cytomegalovirus promoter. Using a mouse monoclonal antibody and a fluorescein isothiocyanate (FITC) labeled antimouse antibody to confirm the expression of the NIS protein of infected tumor cells by immunofluorescence. In vitro iodide uptake experiments were carried out on BacNIS-infected tumor cells to further characterize the BacNIS virus, and the cell killing with 131I and clonogenic assay were performed on BacNIS-infected cell to observe the selective killing effect of 131I on NIS-expressing cells. Results: Infection of thyroid cancer cells (FTC-133, W3) with BacNIS resulted in elevating perchlorate-sensitive 125I uptake of these cells to a higher level than that in noninfected cells. But 125I uptake of 8505C was very low. It was demonstrated that the BacNIS vector did function in tumor cells. In addition, BacNIS-infected tumor cells were selectively killed by exposure to 131I, as revealed by clonogenic assays and the cell-killing rate was higher than that in nontreated tumors. Conclusion: BacNIS is very efficient in triggering iodide uptake of infected tumor cell, and it is outlining the potential of this novel cancer gene therapy. (authors)