Hybrid spherical nucleotide nanoparticles can enhance the synergistic anti-tumor effect of CTLA-4 and PD-1 blockades.
Biomater Sci
; 8(17): 4757-4766, 2020 Sep 07.
Article
en En
| MEDLINE
| ID: mdl-32840510
ABSTRACT
Combined blockades of CTLA-4 and PD-1 can yield better overall complementary clinical outcomes than individual blockades, but the response rates are still relatively low. To investigate the anti-tumor effects of various combined strategies, we designed various spherical nucleotide nanoparticles (SNPs) loaded with CTLA-4 aptamer (cSNPs), PD-1 siRNA (pSNPs) or both (hybrid SNPs, or hSNPs). The results demonstrated that hSNPs could promote significantly stronger anti-tumor immune responses in a nonredundant fashion than the mixture of pSNPs and cSNPs (pSNPs & cSNPs). We reasoned that this is because all individual immune cells could receive both CTLA-4 and PD-1 blockades when they engulfed hSNPs, but it is much less likely that individual immune cells could receive both CTLA-4 and PD-1 blockades as many of them may not take both pSNPs and cSNPS from pSNPs & cSNPs. Further results revealed that the synergistic immune stimulatory effects of CTLA-4 and PD-1 blockades in the form of hSNPs were at least partly through regulating the immune suppressive function of both Tregs and TIM3+ exhausted-like CD8 T cells and allowing effector T cells to expand. This mechanism is not identical to earlier reported mechanisms of CTLA-4 and PD-1 blockades.
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1
Bases de datos:
MEDLINE
Asunto principal:
Nanopartículas
/
Receptor de Muerte Celular Programada 1
Idioma:
En
Revista:
Biomater Sci
Año:
2020
Tipo del documento:
Article
País de afiliación:
China