Combination of STING and TLR 7/8 Agonists as Vaccine Adjuvants for Cancer Immunotherapy.
DMXAA
STING
cancer immunotherapy
cancer vaccine
toll-like receptors
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
11 Dec 2022
11 Dec 2022
Historique:
received:
14
11
2022
revised:
30
11
2022
accepted:
07
12
2022
entrez:
23
12
2022
pubmed:
24
12
2022
medline:
24
12
2022
Statut:
epublish
Résumé
Immunostimulatory adjuvants that potently activate antigen-presenting cells and (in turn) prime cytotoxic T cells are a key component of anticancer vaccines. In this study, we investigated a multi-adjuvant approach combining a TLR 7/8 agonist (522) and a STING agonist (DMXAA) to promote enhanced antigen cross-presentation, stimulate specific antitumor T-cell responses, and provide improved anticancer efficacy. In vitro experiments using bone marrow-derived dendritic cells (BMDCs) confirmed enhanced activation with the 522-DMXAA combination based on both co-stimulatory molecule expression and pro-inflammatory cytokine secretion. The immunization of mice with vaccines comprising both 522 and DMXAA resulted in greater antitumor efficacy in B16F10 melanoma and MB49 bladder tumor models relative to mono-agonist vaccines. Flow cytometry-based analysis of immune cells from immunized mice revealed the significant activation of antigen-presenting cells, increased numbers of activated and Ag-specific CD8+ T cells in the spleen and lymph nodes, modest NK cell activation, and an overall reduction in CD206
Identifiants
pubmed: 36551577
pii: cancers14246091
doi: 10.3390/cancers14246091
pmc: PMC9777055
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : R01 CA260825
Pays : United States
Organisme : NCI NIH HHS
ID : CA260825
Pays : United States
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