Abstract
1438
Objectives: Various DNA vaccines have been tried for inhibiting tumor progression with or without success. We demonstrated the effect of combined radioiodine gene therapy to enhance hMUC1 DNA vaccine in an animal cancer model. Methods: We established a stable colon cancer cell line (CT26/hMUC1-hNIS-Fluc: CMNF) expressing the hMUC1, hNIS, and Fluc genes using retro- and lenti virus systems. The in vitro survival rates of cancer cells were determined using clonogenic assay after 131I treatment. We immunized 28 Balb/c mice intramuscularly with pcDNA3.1 or pcDNA3-hMUC1 once a week for 2 weeks. After then, 1×105 CMNF cells were injected subcutaneously into the right thighs of all mice. Twenty-one days after tumor transplantation, 131I or PBS was administered i.p to produce the four groups of Balb/c mice (pcDNA3.1, pcDNA3.1+131I, pcDNA3-hMUC1+PBS, and pcDNA3-hMUC1+131I groups). Tumor progression was monitored by bioluminescent and scintigraphic images and by caliper measurement. Tumor masses were extracted and weighted at 39 days post tumor challenge. Results: We confirmed that CMNF cells highly expressed hMUC1, hNIS and Fluc by FACS, 125I uptake test, and luciferase assay. The survival rate of CMNF was markedly reduced to 14.6±1.5% after 131I treatment compared with the survival rates of parental cells (p<0.001). Compared to pcDNA3.1 group, pcDNA3.1+131I and pcDNA3-hMUC1+PBS groups did not show the inhibition of tumor growth. Tumor growth inhibition was significant only in the pcDNA3-hMUC1+ 131I group at 39 days post challenge compared to other groups (p<0.05). Tumor masses in pcDNA3-hMUC1+ 131I group were smaller than those of the other groups at postmortem examination (p<0.05). Conclusions: This study shows that the weak preventive effect of cancer hMUC1 DNA vaccine can be enhanced by radioiodine gene therapy using sodium iodide symporter.
- Society of Nuclear Medicine, Inc.