Reference - Detail
| RRC ID | 59876 |
|---|---|
| Author | Umemoto S, Haruta M, Sakisaka M, Ikeda T, Tsukamoto H, Komohara Y, Takeya M, Nishimura Y, Senju S. |
| Title | Cancer therapy with major histocompatibility complex-deficient and interferon β-producing myeloid cells derived from allogeneic embryonic stem cells. |
| Journal | Cancer Sci |
| Abstract |
We previously established a method to generate myeloid cells with a proliferative capability from pluripotent stem cells and designated them iPS-ML. Human iPS-ML cells share features with physiological macrophages including the capability to infiltrate into cancer tissues. We observed therapeutic effects of human iPS-ML cells expressing interferon β (iPS-ML/interferon (IFN)-β) in xenograft cancer models. However, assessment of host immune system-mediated therapeutic and adverse effects of this therapy is impossible by xenograft models. We currently evaluated the therapeutic effects of a mouse equivalent of human iPS-ML/IFN, a mouse embryonic stem (ES) cell-derived myeloid cell line producing IFN (ES-ML/IFN). The ES-MLs producing IFN-β (β-ML) and IFN-γ (γ-ML) and originating from E14 ES cells derived from the 129 mouse strain (H-2b ) were generated, and the MHC (H-2Kb , Db , and I-Ab ) genes of the ES-ML/IFN were disrupted using the clustered regularly interspaced short palindromic repeats (CRISPR)/CAS9 method. We used the ES-ML/IFN to treat allogeneic BALB/c mice (H-2d ) transplanted with Colon26 cancer cells. Treatment with β-ML but not with γ-ML cells repressed the growth of colon cancer in the peritoneal cavity and liver. The transferred ES-ML/IFN infiltrated into cancer tissues and enhanced infiltration of T cells into cancer tissues. ES-ML/IFN therapy increased the number of immune cells in the lymphoid organs. Sensitization of both cancer antigen-specific CD8+ T cells and natural killer (NK) cells were enhanced by the therapy, and CD8+ T cells were essential for the therapeutic effect, implying that donor MHC-deficient β-ML exhibited a therapeutic effect through the activation of host immune cells derived from allogeneic recipient mice. The results suggested the usefulness of HLA-deficient human iPS-ML/IFN-β cells for therapy of HLA-mismatched allogeneic cancer patients. |
| Volume | 110(10) |
| Pages | 3027-3037 |
| Published | 2019-10-1 |
| DOI | 10.1111/cas.14144 |
| PMID | 31348591 |
| PMC | PMC6778629 |
| MeSH | Animals CD8-Positive T-Lymphocytes / metabolism Cell Line, Tumor Colonic Neoplasms / immunology Colonic Neoplasms / therapy* Embryonic Stem Cells / cytology* Embryonic Stem Cells / metabolism Female Histocompatibility Antigens / genetics* Humans Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / metabolism Interferon-beta / metabolism* Killer Cells, Natural / metabolism Lymphocytes, Tumor-Infiltrating / metabolism Mice Mice, Inbred BALB C Myeloid Cells / cytology Myeloid Cells / metabolism Myeloid Cells / transplantation* Transplantation, Homologous Xenograft Model Antitumor Assays |
| IF | 4.751 |
| Times Cited | 1 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 5 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| Human and Animal Cells | Colon-26(RCB2657) |