The development of
peptide vaccines aimed at enhancing immune responses against
tumor cells is becoming a promising area of research. Human
telomerase reverse transcriptase (hTERT) is an ideal universal target for novel
immunotherapies against
cancers. The aim of this work was to verify whether the multiple
antigen peptides (MAP) based on HLA-A0201-restricted CTL
epitopes of hTERT could trigger a better and more sustained CTL response and kill multiple types of hTERT-positive
tumor cells in vitro and ex vivo. Dendritic cells (DC) pulsed with MAP based on HLA-A0201-restricted CTL
epitopes of hTERT (hTERT-540, hTERT-865 and hTERT-572Y) were used to evaluate immune responses against various
tumors and were compared to the immune responses resulting from the use of corresponding linear
epitopes and a recombinant adenovirus-hTERT vector. A 4-h standard (51) Cr-release assay and an ELISPOT assay were used for both in vitro and ex vivo analyses. Results demonstrated that targeting hTERT with an adenovector was the most effective way to stimulate a CD8(+) T cell response. When compared with linear hTERT
epitopes, MAP could trigger stronger hTERT-specific CTL responses against
tumor cells expressing hTERT and
HLA-A0201. In contrast, the activated CTL could neither kill the hTERT-negative
tumor cells, such as U2OS cells, nor kill
HLA-A0201 negative cells, such as HepG2 cells. We also found that these
peptide-specific CTL could not kill autologous lymphocytes and DC with low
telomerase activity. Our results indicate that MAP from hTERT can be exploited for
cancer immunotherapy.