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Combination of STING and TLR 7/8 Agonists as Vaccine Adjuvants for Cancer Immunotherapy
Shah, Manan Larson, Peter Shao, Zekun Yu, Daohai Griffith, Thomas S. Ferguson, David Panyam, Jayanth
Shah, Manan
Larson, Peter
Shao, Zekun
Yu, Daohai
Griffith, Thomas S.
Ferguson, David
Panyam, Jayanth
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Journal article
Date
2022-12-11
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Pharmaceutical Sciences
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http://dx.doi.org/10.3390/cancers14246091
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.
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Bhatnagar, S.; Revuri, V.; Shah, M.; Larson, P.; Shao, Z.; Yu, D.; Prabha, S.; Griffith, T.S.; Ferguson, D.; Panyam, J. Combination of STING and TLR 7/8 Agonists as Vaccine Adjuvants for Cancer Immunotherapy. Cancers 2022, 14, 6091. https://doi.org/10.3390/cancers14246091
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Cancers, Vol. 14, Iss. 24
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