RRC ID 72256
著者 Haruta M, Tomita Y, Yuno A, Matsumura K, Ikeda T, Takamatsu K, Haga E, Koba C, Nishimura Y, Senju S.
タイトル TAP-deficient human iPS cell-derived myeloid cell lines as unlimited cell source for dendritic cell-like antigen-presenting cells.
ジャーナル Gene Ther
Abstract We previously reported a method to generate dendritic cell (DC)-like antigen-presenting cells (APC) from human induced pluripotent stem (iPS) cells. However, the method is relatively complicated and laborious. In the current study, we attempted to establish a method through which we could obtain a large number of functional APC with a simple procedure. We transduced iPS cell-derived CD11b(+) myeloid cells with genes associated with proliferative or anti-senescence effects, enabling the cells to propagate for more than 4 months in a macrophage colony-stimulating factor (M-CSF)-dependent manner while retaining their capacity to differentiate into functional APC. We named these iPS cell-derived proliferating myeloid cells 'iPS-ML', and the iPS-ML-derived APC 'ML-DC'. In addition, we generated TAP2-deficient iPS cell clones by zinc finger nuclease-aided targeted gene disruption. TAP2-deficient iPS cells and iPS-ML avoided recognition by pre-activated allo-reactive CD8(+) T cells. TAP2-deficient ML-DC expressing exogenously introduced HLA-A2 genes stimulated HLA-A2-restricted MART-1-specific CD8(+) T cells obtained from HLA-A2-positive allogeneic donors, resulting in generation of MART-1-specific cytotoxic T lymphocyte (CTL) lines. TAP-deficient iPS-ML introduced with various HLA class I genes may serve as an unlimited source of APC for vaccination therapy. If administered into allogeneic patients, ML-DC with appropriate genetic modifications may survive long enough to stimulate antigen-specific CTL and, after that, be completely eliminated. Based on the present study, we propose an APC-producing system that is simple, safe and applicable to all patients irrespective of their HLA types.
巻・号 20(5)
ページ 504-13
公開日 2013-5-1
DOI 10.1038/gt.2012.59
PII gt201259
PMID 22875043
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 3 ATP-Binding Cassette Transporters / genetics* Antigen-Presenting Cells / cytology* Antigen-Presenting Cells / metabolism CD11b Antigen / genetics Cell Differentiation Cell Proliferation Dendritic Cells* / cytology Dendritic Cells* / immunology Dendritic Cells* / metabolism HLA-A2 Antigen / immunology* HLA-A2 Antigen / metabolism Humans Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / immunology Macrophage Colony-Stimulating Factor / metabolism Myeloid Cells / cytology* Myeloid Cells / immunology Myeloid Cells / metabolism T-Lymphocytes, Cytotoxic / immunology T-Lymphocytes, Cytotoxic / metabolism
IF 4.128
リソース情報
ヒト・動物細胞 293T(RCB2202)