RRC ID |
59876
|
著者 |
Umemoto S, Haruta M, Sakisaka M, Ikeda T, Tsukamoto H, Komohara Y, Takeya M, Nishimura Y, Senju S.
|
タイトル |
Cancer therapy with major histocompatibility complex-deficient and interferon β-producing myeloid cells derived from allogeneic embryonic stem cells.
|
ジャーナル |
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.
|
巻・号 |
110(10)
|
ページ |
3027-3037
|
公開日 |
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
|
引用数 |
1
|
リソース情報 |
ヒト・動物細胞 |
Colon-26(RCB2657) |