Combination of STING and TLR 7/8 Agonists as Vaccine Adjuvants for Cancer Immunotherapy

Shubhmita Bhatnagar, Vishnu Revuri, Manan Shah, Peter G Larson, Zekun Shao, Daohai Yu, Swayam Prabha, Thomas S. Griffith, David M Ferguson, Jayanth Panyam

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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+ macrophages. These results were supported by an increase in the levels of IFN-γ and a reduction in IL-10 levels in the sera. Taken together, these findings demonstrate the potential of the TLR7/8 and STING agonist combination as vaccine adjuvants to activate both innate and adaptive immune responses.

Original languageEnglish (US)
Article number6091
JournalCancers
Volume14
Issue number24
DOIs
StatePublished - Dec 2022

Bibliographical note

Funding Information:
Funding support was obtained from the National Cancer Institute (CA260825), National Institute of Health (EB220558), Basser Center (#270162) and OVPR catalytic award, Temple University.

Publisher Copyright:
© 2022 by the authors.

Keywords

  • DMXAA
  • STING
  • cancer immunotherapy
  • cancer vaccine
  • toll-like receptors

PubMed: MeSH publication types

  • Journal Article

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