An inhalable nanoparticulate STING agonist synergizes with radiotherapy to confer long-term control of lung metastases.
Nat Commun
; 10(1): 5108, 2019 11 08.
Article
en En
| MEDLINE
| ID: mdl-31704921
ABSTRACT
Mounting evidence suggests that the tumor microenvironment is profoundly immunosuppressive. Thus, mitigating tumor immunosuppression is crucial for inducing sustained antitumor immunity. Whereas previous studies involved intratumoral injection, we report here an inhalable nanoparticle-immunotherapy system targeting pulmonary antigen presenting cells (APCs) to enhance anticancer immunity against lung metastases. Inhalation of phosphatidylserine coated liposome loaded with STING agonist cyclic guanosine monophosphate-adenosine monophosphate (NP-cGAMP) in mouse models of lung metastases enables rapid distribution of NP-cGAMP to both lungs and subsequent uptake by APCs without causing immunopathology. NP-cGAMP designed for enhanced cytosolic release of cGAMP stimulates STING signaling and type I interferons production in APCs, resulting in the pro-inflammatory tumor microenvironment in multifocal lung metastases. Furthermore, fractionated radiation delivered to one tumor-bearing lung synergizes with inhaled NP-cGAMP, eliciting systemic anticancer immunity, controlling metastases in both lungs, and conferring long-term survival in mice with lung metastases and with repeated tumor challenge.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Radioterapia
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Melanoma Experimental
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Nanopartículas
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Inmunoterapia
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Pulmón
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Neoplasias Pulmonares
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Proteínas de la Membrana
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Células Presentadoras de Antígenos
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Nucleótidos Cíclicos
Límite:
Animals
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos