Identification of human telomerase reverse transcriptase-derived peptides that induce HLA-A24-restricted antileukemia cytotoxic T lymphocytes

Human telomerase reverse transcriptase (hTERT) is considered a potential ta rget for cancer immunotherapy because it is preferentially expressed in mal ignant cells. hTERT-derived peptides carrying motifs for HLA-A24 (HLA-A*240 2), the most common allele among Japanese and also frequently present in pe rsons of European descent, were examined for their capacity to elicit antil eukemia cyto toxic T lymphocytes (CTLs). Two of the 5 peptides tested, VYAE TKHFL and VYG-FVRACL, appeared capable of generating hTERT peptide-specific and HLA-A24-restricted CTLs. The CD8(+) CTL clones specific for these hTER T peptides exerted cytotoxicity against leukemia cells in an HLA-A24-restri cted manner. This cytotoxicity was inhibited by the addition of hTERT pepti de-loaded autologous cells, suggesting that hTERT is naturally processed in leukemia cells and that hTERT-derived peptides are expressed on these cell s and are recognized by CTLs in the context of HLA-A24. Taken together with the currently identified HLA-A2-restricted CTL epitopes derived from hTERT , identification of new CTL epitopes presented by HLA-A24 increases the fea sibility of immunotherapy for leukemia using hTERT-derived peptides. (Blood , 2001;97: 2903-2907) (C) 2001 by The American Society of Hematology.