title: Establishment of a stable T lymphoma cell line transduced with HLA-A*24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring.
abstract: Wilms' tumor gene 1 (WT1) has been proposed as an attractive target for cancer immunotherapy. A natural 9-mer peptide (CYTWNQMNL), which bound to human leukocyte antigen (HLA)-A*24:02, was identified from among WT1-specific cytotoxic T lymphocyte (CTL) epitopes. This natural WT1 CTL epitope peptide was further modified (CMTWNQMNL) to enhance its binding affinity to HLA-A*24:02. This modified WT1 CTL epitope peptide was superior to the natural peptide for inducing HLA-A*24:02-restricted WT1-specific CTLs. Here we induced several WT1 CTLs that reacted with both modified and natural WT1 tetramers from peripheral blood mononuclear cells. Then, T-cell receptor (TCR) genes were isolated from these WT1 CTLs to determine their Vα and Vβ usage. These TCR genes were transduced into human T lymphoma cells to establish a stable cell line, SK37, which expressed a WT1-specific TCR. We confirmed that SK37 cells reacted with both modified and natural WT1 tetramers, which indicated that SK37 cells could be a useful tool for WT1 tetramer reagent quality assurance. One the basis of these findings, we propose that this WT1 tetramer, which was quality-assured using established SK37 cells, will contribute to reliable immunomonitoring of tumor-specific CTL responses of cancer patients who receive WT1-targeted cancer vaccine therapy or TCR-gene therapy.
authors: Division of Cancer Immunology, Medical and Biological Laboratories Co., Ltd., 1063-103, Ohara, Terasawaoka, Ina, Nagano 396-0002, Japan.
authors: Kazue
authors: K
authors: Watanabe
authors: Shingo
authors: S
authors: Toji
authors: Junya
authors: J
authors: Ohtake
authors: Kiichiroh
authors: K
authors: Nakano
authors: Takayuki
authors: T
authors: Satoh
authors: Hidemitsu
authors: H
authors: Kitamura
authors: Takashi
authors: T
authors: Nishimura
mesh_terms: D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D019672:Genes, T-Cell Receptor / Q000235:genetics*; D016162:Genes, Wilms Tumor; D015316:Genetic Therapy; D059871:HLA-A24 Antigen / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D007963:Leukocytes, Mononuclear; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen