Synergistic tumor-cidal effect of combination of hMUC1 vaccination and hNIS radioiodine gene therapy

We developed the combination therapy of hMUC1 vaccination and hNlS radioiodine gene therapy in tumor bearing mice and visualized the anti-tumor effect using molecular imaging. A stable colon cancer cell line (CT26/hMUC1-hNlS-Fluc: CMNF) expressing the hMUC1, hNlS, and Flue genes was established. The in vitro survival rates of CMNF were determined using clonogenic assay after I-131 treatment. Five groups of 28 Balb/c (7mice/group) mice were made after subcutaneously injection of CMNF cells according to treatments (pcDNA3.1+PBS, phMUC1+PBS, pcDNA3.1+I-131, and phMUC1+I-131 groups). After development of xenografted tumor, PBS, MUC1 vaccine, I-131, and MUC1 vaccine + I-131 were administered to the mice. Tumor progression was monitored by using a bioluminescent image and caliper. Thirty-two days after tumor transplantation, we re-challenged CMNF to pcDNA3.1+I-131, and phMUC1 +I-131 groups. We investigated the number of hMUC1-associated CD8+IFN-+ T cells and of cytotoxic T cells (CTLs) activity using splenocytes in treated mice. The in vitro survival rate of CMNF was significantly reduced to 15.31.1 % after I-131 treatment compared with the survival rates of parental cells (p<0.001). Complete tumor growth inhibition was shown in phMUC1+ I-131 group at 48 days post challenge, but not in any monotherapy group (p<0.05). In cases of tumor rechallenging, complete rejection of the tumor occurred in phMUC1 + I-131 group, but not in pcDNA3.1 + I-131 group. The number of hMUC1-associated CD8+ IFN-+ T cells was significantly more increased in phMUC1 +I-131 group compared mono-therapy group (P<0.001). The activity of hMUC1-associated CTLs in was higher than those of monotherapy groups (P<0.005). We found that this combination therapy induced the complete remission, and rejected rechallenged tumor cells in murine colon cancer model. This novel combination therapy strategy has a possibility to be applied in clinical oncology