IL-27-engineered CAR.19-NK-92 cells exhibit enhanced therapeutic efficacy.
Cytotherapy
; 26(11): 1320-1330, 2024 Nov.
Article
em En
| MEDLINE
| ID: mdl-38970613
ABSTRACT
Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells has shown promising results in early-phase clinical studies. However, advancing CAR-NK cell therapeutic efficacy is imperative. In this study, we investigated the impact of a fourth-generation CD19-targeted CAR (CAR.19) coexpressing IL-27 on NK-92 cells. We observed a significant improvement in NK-92 cell proliferation and cytotoxicity activity against B-cell cancer cell lines, both in vitro and in a xenograft mouse B-cell lymphoma model. Our systematic transcriptome analysis of the activated NK-92 CAR variants further supports the potential of IL-27 in fourth-generation CARs to overcome limitations of NK cell-based targeted tumor therapies by providing essential growth and activation signals. Integrating IL-27 into CAR-NK cells emerges as a promising strategy to enhance their therapeutic potential and elicit robust responses against cancer cells. These findings contribute substantially to the mounting evidence supporting the potential of fourth-generation CAR engineering in advancing NK cell-based immunotherapies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Imunoterapia Adotiva
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Ensaios Antitumorais Modelo de Xenoenxerto
/
Receptores de Antígenos Quiméricos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cytotherapy
Assunto da revista:
TERAPEUTICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Reino Unido