An in situ depot for the sustained release of a TLR7/8 agonist in combination with a TGFß inhibitor promotes anti-tumor immune responses.
Nat Commun
; 15(1): 7687, 2024 Sep 03.
Article
en En
| MEDLINE
| ID: mdl-39227589
ABSTRACT
Cancer curing immune responses against heterogeneous solid cancers require that a coordinated immune activation is initiated in the antigen avid but immunosuppressive tumor microenvironment (TME). The plastic TME, and the poor systemic tolerability of immune activating drugs are, however, fundamental barriers to generating curative anticancer immune responses. Here, we introduce the CarboCell technology to overcome these barriers by forming an intratumoral sustained drug release depot that provides high payloads of immune stimulatory drugs selectively within the TME. The CarboCell thereby induces a hot spot for immune cell training and polarization and further drives and maintains the tumor-draining lymph nodes in an anticancer and immune activated state. Mechanistically, this transforms cancerous tissues, consequently generating systemic anticancer immunoreactivity. CarboCell can be injected through standard thin-needle technologies and has inherent imaging contrast which secure accurate intratumoral positioning. In particular, here we report the therapeutic performance for a dual-drug CarboCell providing sustained release of a Toll-like receptor 7/8 agonist and a transforming growth factor-ß inhibitor in preclinical tumor models in female mice.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Factor de Crecimiento Transformador beta
/
Preparaciones de Acción Retardada
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Receptor Toll-Like 7
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Receptor Toll-Like 8
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Microambiente Tumoral
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Dinamarca