Generation of highly proliferative, rejuvenated cytotoxic T cell clones through pluripotency reprogramming for adoptive immunotherapy.
Mol Ther
; 29(10): 3027-3041, 2021 10 06.
Article
em En
| MEDLINE
| ID: mdl-34023508
Adoptive immunotherapy has emerged as a powerful approach to cure cancer and chronic infections. Currently, the generation of a massive number of T cells that provide long-lasting immunity is challenged by exhaustion and differentiation-associated senescence, which inevitably arise during in vitro cloning and expansion. To circumvent these problems, several studies have proposed an induced pluripotent stem cell (iPSC)-mediated rejuvenation strategy to revitalize the exhausted/senescent T cell clones. Because iPSC-derived cytotoxic T lymphocytes (iPSC-CTLs) generated via commonly used monolayer systems have unfavorable, innate-like features such as aberrant natural killer (NK) activity and limited replication potential, we modified the redifferentiation culture to generate CD8αß+CD5+CCR7+CD45RA+CD56--adaptive iPSC-CTLs. The modified iPSC-CTLs exhibited early memory phenotype, including high replicative capacity and the ability to give rise to potent effector cells. In expansion culture with an optimized cytokine cocktail, iPSC-CTLs proliferated more than 1015-fold in a feeder-free condition. Our redifferentiation and expansion package of early memory iPSC-CTLs could supply memory and effector T cells for both autologous and allogeneic immunotherapies.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Citotóxicos
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Biomarcadores
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Imunoterapia Adotiva
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Técnicas de Cultura de Células
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Células-Tronco Pluripotentes Induzidas
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Neoplasias
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Mol Ther
Assunto da revista:
BIOLOGIA MOLECULAR
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TERAPEUTICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão