Experimental study of targeted radiotherapy by delivering recombinant baculovirus encoding sodium/iodide symporter gene into tumor

Abstract

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Objectives: To investigate the feasibility of tumor radiotherapy by delivering baculoviral vector encoding human sodium/iodide symporter (NIS) gene into tumor cells. Methods: The recombinant baculovirus encoding human NIS gene with cytomegalovirus promoter (Bac-NIS) was constructed according to Bac-to-Bac protocol. Tumor cell lines HepG2 (liver), 8505C (thyroid), A549 (lung) and FTC-133(thyroid) and were infected with Bac-NIS. The presence of the NIS protein was then detected by immunofluorescence using Anti-NIS Antibody. To further characterize the Bac-NIS virus, the iodide uptake experiments in the presence of various concentrations of NaClO4 and kinetics of iodide uptake experiments were carried out on Bac-NIS-infected tumor cells. After 131I treatment, in vitro cell killing with 131I and clonogenic assay were performed to demonstrate whether it was possible to obtain cell killing with the Bac-NIS-radioactive iodide system. And 131I imaging was carried out in the nude mice model bearing FTC-133 tumor. Results: We constructed a recombinant baculovirus encoding the human NIS gene with cytomegalovirus promoter. 125I uptake in tumor cells infected by Bac-NIS was higher than that in noninfected cell. Clonogenic assays showd that Bac-NIS -infected tumor cells were selectively killed when exposed to 131I. To assess the 131I uptake of infected tumor in vivo, we injected the Bac-NIS vector in human tumors established with FTC-133 in nude mice. Bac-NIS-treated tumors could specifically accumulate more 131I than controlled tumor when examined 4 days after intratumoral injection. Conclusions: The research indicated that Bac-NIS was efficient in triggering significant iodide uptake by tumor, outlining the potential of this novel cancer gene therapy for targeted radiotherapy.

Research Support (if any): National Natural Science Foundation of China (No. 30570525).Science and Technology Foundation of Shanghai(02QMB1405)