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

• Published in: Blood Vol. 97; no. 9; pp. 2903 - 2907
• Main Authors: Arai, Junko, Yasukawa, Masaki, Ohminami, Hideki, Kakimoto, Miki, Hasegawa, Atsuhiko, Fujita, Shigeru
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.05.2001; The Americain Society of Hematology
• Subjects: Antineoplastic agents; Biological and medical sciences; Cell Line; Cytotoxicity, Immunologic; DNA-Binding Proteins; HLA-A Antigens - immunology; HLA-A24 Antigen; Humans; Immunotherapy; Leukemia - immunology; Medical sciences; Peptide Fragments - immunology; Pharmacology. Drug treatments; RNA; T-Lymphocytes, Cytotoxic - immunology; Telomerase - immunology; Asia; Japan; Antineoplastic agent; Human; HLA-System; RNA-directed DNA polymerase; Immune response; Antigenic determinant; Peptides; Enzyme; Transferases; Leukemia; Major histocompatibility system; Cytotoxicity; Malignant hemopathy; Nucleotidyltransferases; Treatment; HLA-A-Locus; Histocompatibility restriction; Immunotherapy; Cytotoxic T lymphocyte; Telomerase; Class I histocompatibility antigen
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V97.9.2903

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.