RRC ID |
72599
|
著者 |
Haga E, Endo Y, Haruta M, Koba C, Matsumura K, Takamatsu K, Ikeda T, Nishimura Y, Senju S.
|
タイトル |
Therapy of peritoneally disseminated colon cancer by TAP-deficient embryonic stem cell-derived macrophages in allogeneic recipients.
|
ジャーナル |
J Immunol
|
Abstract |
We established a method to generate a large quantity of myeloid lineage cells from mouse embryonic stem (ES) cells, termed ES cell-derived proliferating myeloid cell lines (ES-ML). ES-ML continuously proliferated in the presence of M-CSF and GM-CSF. ES-ML genetically modified to express an anti-HER2 (neu) mAb single-chain V region fragment reduced the number of cocultured mouse Colon-26 cancer cells expressing HER2. Stimulation of ES-ML with IFN-γ plus LPS or TNF resulted in almost complete killing of the Colon-26 cells by the ES-ML, and the cytotoxicity was mediated, in part, by NO produced by ES-ML. When ES-ML were injected into mice with i.p. established Colon-26 tumors, they efficiently infiltrated the tumor tissues. Injection of ES-ML with rIFN-γ and LPS inhibited cancer progression in the mouse peritoneal cavity. Coinjection of TNF-transfected or untransfected ES-ML with rIFN-γ inhibited cancer growth and resulted in prolonged survival of the treated mice. In this experiment, transporter associated with Ag processing (TAP)1-deficient ES-ML exhibited therapeutic activity in MHC-mismatched allogeneic recipient mice. Despite the proliferative capacity of ES-ML, malignancy never developed from the transferred ES-ML in the recipient mice. In summary, TAP-deficient ES-ML with anticancer properties exhibited a therapeutic effect in allogeneic recipients, suggesting the possible use of TAP-deficient human-induced pluripotent stem cell-derived proliferating myeloid cell lines in cancer therapy.
|
巻・号 |
193(4)
|
ページ |
2024-33
|
公開日 |
2014-8-15
|
DOI |
10.4049/jimmunol.1303473
|
PII |
jimmunol.1303473
|
PMID |
25031460
|
MeSH |
ATP-Binding Cassette Transporters / genetics*
Animals
Antibodies, Monoclonal / immunology
Cell Differentiation / immunology
Cell Line, Tumor
Colonic Neoplasms / immunology
Colonic Neoplasms / therapy*
Cytotoxicity, Immunologic
Embryonic Stem Cells / immunology*
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
Interferon-gamma / pharmacology
Lipopolysaccharides
Macrophages / immunology*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Pluripotent Stem Cells / immunology
Receptor, ErbB-2 / immunology
Single-Chain Antibodies / immunology
Transplantation, Homologous
|
IF |
4.886
|
リソース情報 |
ヒト・動物細胞 |
Colon-26(RCB2657) |