Combined Telomerase Inhibition and Immunotherapy in the Prevention and Treatment of Mammary Carcinomas

摘要

To determine antitumor immunity in MMT mice that are deficient for telomerase activity, we immunized MMT, G0 and G1 to G4 mTERC-/-MMT mice with DC/tumor fusion vaccine (FC/MMT). Vaccination of MMT, G0 and G1 to G4 mTERC-/- MMT mice induced CTL that lysed MUC1-positive tumor cells, suggesting that the cellular immunity is not affected by telomerase inactivity, at least in the G1 and G2 mTERC-/-MMT mice. The induction of CTL in these mice translated into delayed appearance of mammary carcinomas. The latency time for the mammary tumors in MMT, G0 and G1 to G4 mTERC-/-MMT mice immunized with FC/MUC1 were 112.4 plus or minus 10.4, 113.6 plus or minus 8.4, 136.3 plus or minus 10, 144.3 plus or minus 12.7, 158.7 plus or minus 15.7 and 247.3 days, respectively. The difference of latency time between immunized and non- immunized mice was statistically significant in all groups except the G4 group. In addition, T cell proliferation and cell division in G1 and G3 mTERC-/-MMT mice were comparable with those from MMT and G0 mice as demonstrated by standard isotope incorporation and CFSE labeling. Taken together, these results indicate that telomerase inactivity enhances the antitumor immunity, at least in the first and second generations of mTERC-/-MMT mice.