Synergistic tumoricidal effect of combined hMUC1 vaccination and hNIS radioiodine gene therapy

Abstract

We examined the merits of combinatorial hMUC1 vaccination and hNIS radioiodine gene therapy and evaluated its tumoricidal effects in an animal tumor model. CMNF (CT26 expressing hMUC1, hNIS, and firefly luciferase) cells were transplanted into 28 mice, and 4 and 11 days after tumor challenge, tumor-bearing mice were immunized i.m. with pcDNA3.1 or pcDNA-hMUC1 vaccine and subsequently administered PBS or 131I i.p. [four groups (7 mice per group): pcDNA3.1 + PBS, phMUC1 + PBS, pcDNA3.1 + 131I, and phMUC1 + 131I groups]. Thirty-two days after tumor challenge, we rechallenged mice in the pcDNA3.1 + 131I and phMUC1 + 131I groups with CMNF cells. Tumor progression and tumor-free mice (%) were monitored by bioluminescence. We investigated hMUC1-associated immune response generated by combination therapy. Marked tumor growth inhibition was observed in the phMUC1 + 131I group by bioluminescence at 32 days after tumor challenge. Mice in phMUC1 + 131I group showed complete hMUC1-expressing tumor suppression after tumor rechallenge, whereas mice in the pcDNA3.1 + 131I group did not. The tumor-free mice (%) were much higher in the phMUC1 + 131I group than in the other three groups. Levels of hMUC1-associated CD8+IFN-γ+ T cells were higher in the phMUC1 + 131I group than in the other three groups. hMUC1-loaded CD11+ cells in the phMUC1 + 131I group were found to be most effective at generating hMUC1-associated CD8+IFN-γ+ T cells. The activities of hMUC1-associated cytotoxic T cells in the phMUC1 + 131I group were higher than in the other three groups. Our data suggest that phMUC1 + 131I combination therapy synergistically generates marked tumoricidal effects against established hMUC1-expressing cancers.