Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors.
Cell
; 167(2): 419-432.e16, 2016 Oct 06.
Article
en En
| MEDLINE
| ID: mdl-27693353
ABSTRACT
Redirecting T cells to attack cancer using engineered chimeric receptors provides powerful new therapeutic capabilities. However, the effectiveness of therapeutic T cells is constrained by the endogenous T cell response certain facets of natural response programs can be toxic, whereas other responses, such as the ability to overcome tumor immunosuppression, are absent. Thus, the efficacy and safety of therapeutic cells could be improved if we could custom sculpt immune cell responses. Synthetic Notch (synNotch) receptors induce transcriptional activation in response to recognition of user-specified antigens. We show that synNotch receptors can be used to sculpt custom response programs in primary T cells they can drive a la carte cytokine secretion profiles, biased T cell differentiation, and local delivery of non-native therapeutic payloads, such as antibodies, in response to antigen. SynNotch T cells can thus be used as a general platform to recognize and remodel local microenvironments associated with diverse diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T CD4-Positivos
/
Linfocitos T CD8-positivos
/
Receptores Notch
/
Ingeniería Celular
/
Receptores Artificiales
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos