Human sodium iodide symporter gene adjunctive radiotherapy to enhance the preventive effect of hMUC1 DNA vaccine

Abstract

We demonstrate the use of combination therapy to overcome the limitations of cancer DNA vaccines by adding radioiodine gene therapy in an animal cancer model. We established a stable cell line (CT26/hMUC1-hNIS-Fluc: CMNF) expressing the hMUC1, hNIS and Fluc genes using a retro- and lentivirus system. The survival rates (%) of CMNF cells were determined using clonogenic assays after 131I treatment. After i.m. immunization to 4 groups of Balb/c mice (pcDNA3.1, pcDNA3.1+131I, pcDNA3-hMUC1+PBS and pcDNA3-hMUC1+ 131I groups) with pcDNA3-hMUC1 or pcDNA3.1 once a week for 2 weeks, 1 × 105 CMNF cells were injected s.c. into the right thighs of mice in each group. Twenty-one days after tumor transplantation, 131I was administered i.p. to the pcDNA3.1+131I and pcDNA3-hMUC1+ 131I groups. Tumor progression was monitored in the 4 groups by bioluminescent and scintigraphic imaging and by taking caliper measurements. Tumor masses were extracted and weighted at 39 days post-tumor challenge. We confirmed that CMNF cells highly express hMUC1, hNIS and Fluc by FACS, 125I uptake, and luciferase assay. The survival rates of CMNF were markedly reduced to (14.6 ± 1.5)% after 131I treatment compared with the survival rates of parental cells (p < 0.001). Tumor growth inhibition was significant only in the pcDNA3-hMUC1+ 131I group at 39 days post challenge. Tumor masses in pcDNA3-hMUC1+ 131I group were smaller than those of the other groups. This study shows that the weak preventive effects of cancer DNA vaccine can be overcome by radioiodine gene therapy utilizing sodium iodide symporter. © 2007 Wiley-Liss, Inc.