Constitutive expression of interleukin-27 diminishes proinflammatory cytokine production without impairing effector function of engineered T cells.
Cytotherapy
; 25(9): 913-919, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37306644
ABSTRACT
Immunomodulatory cytokines can alter the tumor microenvironment and promote tumor eradication. Interleukin (IL)-27 is a pleiotropic cytokine that has potential to augment anti-tumor immunity while also facilitating anti-myeloma activity. We engineered human T cells to express a recombinant single-chain (sc)IL-27 and a synthetic antigen receptor targeting the myeloma antigen, B-cell maturation antigen, and evaluated the anti-tumor function of T cells bearing scIL-27 in vitro and in vivo. We discovered that T cells bearing scIL-27 sustained anti-tumor immunity and cytotoxicity yet manifested a profound reduction in pro-inflammatory cytokines granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha. IL-27-expressing T cells therefore present a potential avenue to avert treatment-related toxicities commonly associated with engineered T-cell therapy due to the reduced pro-inflammatory cytokine profile.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interleucina-27
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Neoplasias
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article