title: A HLA-A2-restricted CTL epitope induces anti-tumor effects against human lung cancer in mouse xenograft model.
abstract: Cancer immunotherapy is attractive for antigen-specific T cell-mediated anti-tumor therapy, especially in induction of cytotoxic T lymphocytes. In this report, we evaluated human CTL epitope-induced anti-tumor effects in human lung cancer xenograft models. The tumor associated antigen L6 (TAL6) is highly expressed in human lung cancer cell lines and tumor specimens as compared to normal lung tissues. TAL6 derived peptides strongly inhibited tumor growth, cancer metastasis and prolonged survival time in HLA-A2 transgenic mice immunized with a formulation of T-helper (Th) peptide, synthetic CpG ODN, and adjuvant Montanide ISA-51 (ISA-51). Adoptive transfer of peptide-induced CTL cells from HLA-A2 transgenic mice into human tumor xenograft SCID mice significantly inhibited tumor growth. Furthermore, combination of CTL-peptide immunotherapy and gemcitabine additively improved the therapeutic effects. This pre-clinical evaluation model provides a useful platform to develop efficient immunotherapeutic drugs to treat lung cancer and demonstrates a promising strategy with benefit of antitumor immune responses worthy of further development in clinical trials.
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.|Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yuh-Pyng
authors.initials: YP
authors.lastname: Sher
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Su-I
authors.initials: SI
authors.lastname: Lin
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
authors.forename: I-Hua
authors.initials: IH
authors.lastname: Chen
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
authors.forename: Hsin-Yu
authors.initials: HY
authors.lastname: Liu
authors.affiliation: Division of Hematology and Oncology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chen-Yuan
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Pathology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: I-Ping
authors.initials: IP
authors.lastname: Chiang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Steve
authors.initials: S
authors.lastname: Roffler
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.|National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
authors.forename: Hsin-Wei
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.|National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D058501:Enzyme-Linked Immunospot Assay; D000939:Epitopes / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D016513:Mice, SCID; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000954:Antigens, Surface; D000939:Epitopes; D015789:HLA-A2 Antigen; D009363:Neoplasm Proteins; C074075:TM4SF1 protein, human; D007371:Interferon-gamma
keywords: TAL6; cytotoxic T lymphocytes; lung cancer; peptide