The optimal interval for dendritic cell vaccination following adoptive T cell transfer is important for boosting potent anti-tumor immunity

The gradual induction of immune responses by dendritic cell (DC) vaccination or the rapid decrease of adoptively transferred T cells may be major limitations in complete treatment of established tumors by active or passive immunization. The numbers of carcinoembryonic antigen (CEA)-specific T cells increased on 7th day and decreased from 2 weeks after repeated vaccination with CEA-peptide-pulsed DCs. Adoptively transferred CEA-specific T cells were detectable on day 1 and reached their peak by day 4, and thereafter decreased. On the basis of these results, a combined immunotherapy of DC vaccination following adoptive T cell transfer was performed to overcome these limitations of each modality. The injection of DCs within 1 day after adoptive T cell transfer showed a synergistic effect. However, when the DC vaccine was administered on day 3 or 7, CEA-specific T cells gradually declined. This concomitant immunization significantly inhibited the tumor growth than the DC vaccine administered on day 3 or 7 in 10 days tumor model. Moreover, the concomitant immunization showed potent anti-tumor effects resulting in complete inhibition of tumor growth in 2 days tumor model. These results suggest that the optimal interval for the DC vaccination following adoptive T cell transfer is important for boosting antigen-specific T cell responses and this combined immunotherapy may provide a potent therapeutic strategy for cancer treatment.