Efficient Regeneration of Human Vα24+ Invariant Natural Killer T Cells and Their Anti-Tumor Activity In Vivo.
Stem Cells
; 34(12): 2852-2860, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27422351
ABSTRACT
Reprogramming of antigen-specific T lymphocytes into induced pluripotent stem cells (iPSCs) and their subsequent re-differentiation has enabled expansion of functional T lymphocytes in vitro, thus opening up new approaches for immunotherapy of cancer and other diseases. In this study, we have established a robust protocol to reprogram human invariant NKT (Vα24+ iNKT) cells, which have been shown to act as cellular adjuvants and thus exert anti-tumor activity in mice and humans, and to re-differentiate the iNKT cell-derived iPSCs into functional iNKT cells. These iPSC-derived iNKT cells (iPS-Vα24+ iNKT cells) can be activated by ligand-pulsed dendritic cells (DCs) and produce a large amount of interferon-γ upon activation, as much as parental Vα24+ iNKT cells, but exhibit even better cytotoxic activity against various tumor cell lines. The iPS-Vα24+ iNKT cells possess significant anti-tumor activity in tumor-bearing mice and can activate autologous NK cells upon activation by ligand-pulsed DCs in the NOG mouse model in vivo, further extending their therapeutic potential. This study thus provides a first proof of concept for the clinical application of human iPS-Vα24+ iNKT cells for cancer immunotherapy. Stem Cells 2016;342852-2860.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regeneração
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Receptores de Antígenos de Linfócitos T
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Células T Matadoras Naturais
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Antineoplásicos
Tipo de estudo:
Guideline
Limite:
Animals
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Humans
Idioma:
En
Revista:
Stem Cells
Ano de publicação:
2016
Tipo de documento:
Article