RRC ID 72599
Author Haga E, Endo Y, Haruta M, Koba C, Matsumura K, Takamatsu K, Ikeda T, Nishimura Y, Senju S.
Title Therapy of peritoneally disseminated colon cancer by TAP-deficient embryonic stem cell-derived macrophages in allogeneic recipients.
Journal 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.
Volume 193(4)
Pages 2024-33
Published 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
Human and Animal Cells Colon-26(RCB2657)