RRC ID |
64099
|
著者 |
Watanabe K, Toji S, Ohtake J, Nakano K, Satoh T, Kitamura H, Nishimura T.
|
タイトル |
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.
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ジャーナル |
Biomed Res
|
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.
|
巻・号 |
34(1)
|
ページ |
41-50
|
公開日 |
2013-2-1
|
DOI |
10.2220/biomedres.34.41
|
PII |
DN/JST.JSTAGE/biomedres/34.41
|
PMID |
23428979
|
MeSH |
Cancer Vaccines
Cell Line, Tumor*
Cloning, Molecular
Epitopes, T-Lymphocyte / genetics
Epitopes, T-Lymphocyte / immunology
Genes, T-Cell Receptor / genetics*
Genes, Wilms Tumor*
Genetic Therapy
HLA-A24 Antigen / immunology*
Humans
Immunotherapy
Leukocytes, Mononuclear
Lymphoma, T-Cell / genetics*
Lymphoma, T-Cell / immunology
T-Lymphocytes, Cytotoxic / immunology
T-Lymphocytes, Cytotoxic / metabolism
Transduction, Genetic*
|
IF |
1.429
|
リソース情報 |
ヒト・動物細胞 |
Jurkat |