Generating stem-like memory T cells with antioxidants for adoptive cell transfer immunotherapy of cancer.
Methods Enzymol
; 631: 137-158, 2020.
Article
em En
| MEDLINE
| ID: mdl-31948545
Among the multiple factors that are responsible for the success of adoptive cell transfer (ACT) immunotherapy for cancer, the differentiation status of the in vitro expanded T cell product at the time of transfer seems to play a major role. In particular, less differentiated memory CD8+ T cells endowed with self-renewing capacity and multipotency exert the most potent antitumor activity. To this aim, expansion protocols that generate sufficient numbers of tumor-specific CD8+ T cells with superior capacity to persist in vivo following ACT are needed. We describe a procedure for the differentiation of TCF-1+ stem-like CD8+ memory T cells from peripheral blood naïve precursors that takes advantage of the use of antioxidants, in particular N-acetylcysteine (NAC), in combination with T cell receptor stimulation and proinflammatory cytokines. We additionally describe how to conduct in vitro assays to test the stem-like features of the generated cells at the phenotypic, functional and metabolic level. Balancing the oxidative metabolism by the addition of antioxidants during in vitro manipulation of CD8+ T cells results in the generation of cell products with potent antitumor characteristics following ACT.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Acetilcisteína
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Testes Imunológicos de Citotoxicidade
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Imunoterapia Adotiva
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Linfócitos T CD8-Positivos
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Memória Imunológica
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Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article