Induction Of Anti-tumor Immunity Using A Dendritic Cell-targeting Adenovirus Encoding Telomerase Reverse Transcriptase

Telomerase Reverse Transcriptase (TERT), the catalytic subunit of telomerase, is elevated in most tumors of human and murine origin. Thus, it may serve as a universal tumor antigen candidate for immunotherapy of cancer. It is conceivable that the breaking of immune tolerance of TERT should be useful approach to cancer therapy by active immunity. In the present study, we constructed a replication-deficient recombinant adenovirus encoding mouse TERT (AdT) in an E. Coli-based homologous recombination system. Later, the adenovirus was conjugated with mannan (AdT-m), as a vaccine. In addition, adenovirus without mannan (AdT), the null adenovirus (Adnull) and PBS alone were used as controls. We found this vaccine could induce anti-tumor activity against telomerase (+) tumors of different histological origins when applied in vivo. However, no such effects were observed in control groups. In an attempt to explore the possible underlying mechanism, we found that both CD8 and CD4 T cells were responsible for the anti-tumor immunity. In the in vivo deletion study, deletion of either CD4 or CD8 cells abrogated the anti-tumor immunity. The adoptive transfer of CD4-depleted (CD8+) or CD8-depleted (CD4+) T cells isolated from mice vaccinated with AdT-m showed the anti-tumor activity. The anti-tumor efficacy observed might be due to the preferred presentation of the foreign antigen to dendritic cells (DCs)mediated by the mannan. Taken together, these findings may provide a new vaccine strategy for the treatment of different TERT~+ tumors through the induction of anti-tumor immunity against TERT.