title: A novel HLA-A2-restricted CTL epitope of tumor-associated antigen L6 can inhibit tumor growth in vivo.
abstract: Vaccines utilizing cytotoxic T lymphocyte (CTL) epitopes are promising for the treatment of cancer and chronic infectious diseases. Tumor-associated antigen L6 (TAL6) is overexpressed in some epithelial cancer cells. In this report, we detected TAL6 expression in breast cancer tissue using quantitative reverse-transcriptase-polymerase chain reaction. We found that >80% of breast tumor tissue highly expressed TAL6 compared with adjacent normal breast tissue. To identify CTL epitopes from TAL6, we synthesized 18 peptides for HLA-A2-binding assay based on the MHC-binding motif using 4 computer prediction programs. Positive binders identified by ELISA were immunized in HLA-A2 transgenic (A2 Tg) mice. Two peptides, peptide 2 and peptide 5, induced T-cell responses in A2 Tg mice. To confirm whether these peptides could be processed and presented to induce T-cell responses in vivo, A2 Tg mice were immunized with plasmid DNA encoding TAL6. We found that both peptides 2 and 5 stimulated splenocytes from TAL6-immunized mice to secrete interferon-γ. However, only peptide 5 could induce expression of the cytolytic molecule CD107a on CD8+ T cells after immunization. Furthermore, peptide 5-immunized A2 Tg mice could inhibit the growth of TAL6-positive tumors (EL4/TAL6/HLA-A2) in A2 Tg mice but not in wild-type mice. These results demonstrate that the TAL6-derived CTL epitope could induce HLA-A2-restricted immunity against TAL6-expressing tumor cells.
authors.affiliation: Department of Surgery, Cathay General Hospital †Department of Surgery, School of Medicine, Taipei Medical University, Taiwan.
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Tu
authors.forename: Hsing-I
authors.initials: HI
authors.lastname: Huang
authors.forename: Su-I
authors.initials: SI
authors.lastname: Lin
authors.forename: Hsin-Yu
authors.initials: HY
authors.lastname: Liu
authors.forename: Yuh-Pyng
authors.initials: YP
authors.lastname: Sher
authors.forename: Sheng-Kuo
authors.initials: SK
authors.lastname: Chiang
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
authors.forename: Steve
authors.initials: S
authors.lastname: Roffler
authors.forename: Guan-Chin
authors.initials: GC
authors.lastname: Tseng
authors.forename: Hsin-Wei
authors.initials: HW
authors.lastname: Chen
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000954:Antigens, Surface; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D009363:Neoplasm Proteins; D010455:Peptides; C074075:TM4SF1 protein, human