T cells expressing chimeric antigen receptor promote immune tolerance.
JCI Insight
; 2(20)2017 10 19.
Article
em En
| MEDLINE
| ID: mdl-29046484
Cellular therapies based on permanent genetic modification of conventional T cells have emerged as a promising strategy for cancer. However, it remains unknown if modification of T cell subsets, such as Tregs, could be useful in other settings, such as allograft transplantation. Here, we use a modular system based on a chimeric antigen receptor (CAR) that binds covalently modified mAbs to control Treg activation in vivo. Transient expression of this mAb-directed CAR (mAbCAR) in Tregs permitted Treg targeting to specific tissue sites and mitigated allograft responses, such as graft-versus-host disease. mAbCAR Tregs targeted to MHC class I proteins on allografts prolonged islet allograft survival and also prolonged the survival of secondary skin grafts specifically matched to the original islet allograft. Thus, transient genetic modification to produce mAbCAR T cells led to durable immune modulation, suggesting therapeutic targeting strategies for controlling alloreactivity in settings such as organ or tissue transplantation.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Receptores de Antígenos Quiméricos
/
Tolerância Imunológica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos