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Blood, 1 May 2001, Vol. 97, No. 9, pp. 2903-2907
BRIEF REPORT
Identification of human telomerase reverse transcriptase-derived
peptides that induce HLA-A24-restricted antileukemia cytotoxic
T lymphocytes
Junko Arai,
Masaki Yasukawa,
Hideki Ohminami,
Miki Kakimoto,
Atsuhiko Hasegawa, and
Shigeru Fujita
From the First Department of Internal Medicine, Ehime
University School of Medicine, Shigenobu, Ehime, Japan.
Human telomerase reverse transcriptase (hTERT) is considered a
potential target for cancer immunotherapy because it is preferentially expressed in malignant cells. hTERT-derived peptides carrying motifs
for HLA-A24 (HLA-A*2402), the most common allele among Japanese and
also frequently present in persons of European descent, were examined
for their capacity to elicit antileukemia cytotoxic T lymphocytes
(CTLs). Two of the 5 peptides tested, VYAETKHFL and VYGFVRACL, appeared
capable of generating hTERT peptide-specific and HLA-A24-restricted
CTLs. The CD8+ CTL clones specific for these hTERT peptides
exerted cytotoxicity against leukemia cells in an HLA-A24-restricted
manner. This cytotoxicity was inhibited by the addition of hTERT
peptide-loaded autologous cells, suggesting that hTERT is naturally
processed in leukemia cells and that hTERT-derived peptides are
expressed on these cells 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 feasibility
of immunotherapy for leukemia using hTERT-derived peptides.
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