A novel DNA methyltransferase I–derived peptide eluted from soluble HLA‐A0201 induces peptide‐specific, tumor‐directed cytotoxic T cells

• Published in: International journal of cancer 2004-11, Vol.112 (3), p.426-432
• Main Authors: Berg, Martina, Barnea, Eilon, Admon, Arie, Zavazava, Nicholas
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Breast Neoplasms - immunology; Breast Neoplasms - metabolism; cancer vaccine; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases - immunology; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNMT‐1; Female; HLA-A Antigens - immunology; HLA-A Antigens - metabolism; HLA-A2 Antigen - immunology; HLA-B7 Antigen - immunology; Humans; Immunotherapy; Male; Medical sciences; Ovarian Neoplasms - immunology; Ovarian Neoplasms - metabolism; Peptide Fragments - immunology; Peptide Fragments - metabolism; Pharmacology. Drug treatments; Prostatic Neoplasms - immunology; Prostatic Neoplasms - metabolism; soluble HLA; T-Lymphocytes, Cytotoxic - immunology; tumor antigen; Tumor Cells, Cultured; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.20381

MHC peptides derived from tumor‐associated antigens (TAAs) can serve as the basis for the development of immunotherapeutics to treat human malignancies. Previously, we identified novel HLA‐A*0201 (HLA‐A2)–restricted peptides recovered from soluble HLA molecules secreted by human tumor cell lines, transfected with truncated genes of HLA‐A2 and HLA‐B7. Here, 4 candidate peptides eluted from soluble HLA‐A2 were selected on the basis of their precursor proteins being TAAs. Peptide p1028 (GLIEKNIEL), derived from DNA methyltransferase I (DNMT‐1), which is overexpressed in various human tumors, showed the highest affinity to HLA‐A2 and was relatively abundant in the sMHC/peptide complexes of all transfected breast, ovarian and prostate cancer cell lines. Peptide p1028‐specific CTLs were generated in vitro and shown to efficiently lyse not only target cells pulsed with the peptide but also HLA‐A2‐positive breast cancer cell lines MDA‐231 and MCF‐7. The peptide induced IFN‐γ production in CTLs, which were selectively stained by a p1028 tetramer. Since DNMT‐1 is a widely expressed tumor‐associated enzyme, the novel DNMT‐1‐derived, HLA‐A2‐restricted peptide GLIEKNIEL identified here may provide a suitable candidate for a therapeutic cancer vaccine. © 2004 Wiley‐Liss, Inc.