Tandem Chemoimmunotherapy by a Cascade-Responsive Molecular Prodrug.
ACS Chem Biol
; 17(4): 762-767, 2022 04 15.
Article
en En
| MEDLINE
| ID: mdl-35285234
ABSTRACT
The limited therapeutic effects of immunotherapy for most types of cancer stimulates the pursuit for efficient methods to improve its response rate. Herein we report the design and synthesis of a cascade-responsive molecular prodrug for tandem chemoimmunotherapy. This molecular prodrug first releases doxorubicin (DOX) in the mildly acidic tumor microenvironment (TME) to induce immunogenic cell death (ICD) of tumor cells. Caspase 3/7 released during tumor cell apoptosis liberates NLG919 from the prodrug, which inhibits the activity of indoleamine 2,3-dioxygenase (IDO) and results in relief of TME immunosuppression. Meanwhile, tumor-associated antigens and immune stimulatory cytokines released during ICD activate the immune response against the tumor, leading to synergistic chemoimmunotherapy. The efficacy of this prodrug is validated by in vitro and in vivo experiments, demonstrating the success of this strategy for cancer treatment.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Profármacos
/
Dendrímeros
/
Nanopartículas
/
Receptores Quiméricos de Antígenos
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
ACS Chem Biol
Año:
2022
Tipo del documento:
Article
País de afiliación:
China