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J Immunol. 2014 Aug 15;193(4):2024-33. doi: 10.4049/jimmunol.1303473. Epub 2014 Jul 16.

Therapy of peritoneally disseminated colon cancer by TAP-deficient embryonic stem cell-derived macrophages in allogeneic recipients.

Author information

  • 1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
  • 2Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan; and.
  • 3Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan; and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan senjusat@gpo.kumamoto-u.ac.jp.

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.

Copyright © 2014 by The American Association of Immunologists, Inc.

PMID:
25031460
[PubMed - indexed for MEDLINE]
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