Reversal of tumor immune inhibition using a chimeric cytokine receptor.
Mol Ther
; 22(6): 1211-1220, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24732709
The success of adoptively transferred tumor-directed T cells requires them to survive and expand in vivo. Most tumors, however, employ immune evasion mechanisms, including the production of inhibitory cytokines that limit in vivo T-cell persistence and effector function. To protect tumor-directed T cells from such negative influences, we generated a chimeric cytokine receptor in which the interleukin (IL) 4 receptor exodomain was fused to the IL7 receptor endodomain. We thereby inverted the effects of tumor-derived IL4 so that the proliferation and activation of tumor directed cytotoxic T cells was enhanced rather than inhibited in the tumor microenvironment, resulting in superior antitumor activity. These transgenic T cells were only activated in the tumor environment since triggering required exposure to both tumor antigen (signal 1) and tumor-derived IL4 (signal 2). This selectivity supports future clinical adaptation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Receptores de Interleucina-7
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Subunidade alfa de Receptor de Interleucina-4
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Microambiente Tumoral
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Neoplasias Experimentais
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Ther
Ano de publicação:
2014
Tipo de documento:
Article