Therapeutic Targeting of Follicular T Cells with Chimeric Antigen Receptor-Expressing Natural Killer Cells.
Cell Rep Med
; 1(1)2020 04 21.
Article
em En
| MEDLINE
| ID: mdl-32864635
ABSTRACT
Follicular helper T cells (TFH) are critical for vaccine and infection elicitation of long-lived humoral immunity, but exaggerated TFH responses can promote autoimmunity and other pathologies. It is unfortunate that no clinical interventions exist for the selective depletion of follicular T cells to alleviate these diseases. We engineered a chimeric antigen receptor (CAR) facilitating the specific targeting of cells with high expression levels of human programmed cell death protein 1 (PD-1), a cardinal feature of follicular T cells. CAR-expressing human natural killer (NK) cells robustly and discriminately eliminated PD-1high follicular human T cells in vitro and in a humanized mouse model of lupus-like disease while sparing B cells and other PD-1low T cell subsets, including regulatory T cells. These results establish a strategy for specific targeting of PD-1high T cells that can be advanced as a clinical tool for the selective depletion of pathogenic follicular T cells or other PD-1high target cells in certain disease states.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
7_ODS3_muertes_prevenibles_nacidos_ninos
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Linfócitos T
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Receptores de Antígenos Quiméricos
Limite:
Adult
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Animals
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Child
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Child, preschool
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Female
/
Humans
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Male
Idioma:
En
Revista:
Cell Rep Med
Ano de publicação:
2020
Tipo de documento:
Article