L-Pampo?, a Novel TLR2/3 Agonist, Acts as a Potent Cancer Vaccine Adjuvant by Activating Draining Lymph Node Dendritic Cells

Cancers(2023)

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摘要
Simple Summary Toll-like receptor (TLR) agonists induce strong immune responses, which are used as an effective adjuvant system for vaccine development. L-pampo & TRADE; is our innovative adjuvant system containing TLR2 and TLR3 agonists, and it provides robust humoral and cellular immune responses against infectious diseases. Cancer vaccines are a type of cancer immunotherapy that activate the host immune system to recognize and eliminate cancer cells. Here, we investigate the anti-tumor efficacy and the mechanism of action of vaccines formulated with L-pampo & TRADE;. We demonstrate that L-pampo & TRADE; directly stimulates the maturation and function of dendritic cells, which are essential antigen-presenting cells. Additionally, the vaccine formulated with L-pampo & TRADE; induces the recruitment of dendritic cells into lymph nodes, where they prime antigen-specific T-cell responses and induce potent anti-tumor effects. Interestingly, combining vaccines formulated with L-pampo & TRADE; with immune checkpoint inhibitors induces a synergistic anti-tumor effect, indicating that L-pampo & TRADE; can be a powerful cancer vaccine adjuvant and a potent partner for combination immunotherapy. TLR agonists have emerged as an efficient cancer vaccine adjuvant system that induces robust immune responses. L-pampo & TRADE;, a proprietary vaccine adjuvant of TLR2 and TLR3 agonists, promotes strong humoral and cellular immune responses against infectious diseases. In this study, we demonstrate that vaccines formulated with L-pampo & TRADE; affect the recruitment and activation of dendritic cells (DCs) in draining lymph nodes (dLNs) and leading to antigen-specific T-cell responses and anti-tumor efficacy. We analyzed DC maturation and T-cell proliferation using flow cytometry and ELISA. We determined the effect of L-pampo & TRADE; on DCs in dLNs and antigen-specific T-cell responses using flow cytometric analysis and the ELISPOT assay. We employed murine tumor models and analyzed the anti-tumor effect of L-pampo & TRADE;. We found that L-pampo & TRADE; directly enhanced the maturation and cytokine production of DCs and, consequently, T-cell proliferation. OVA or OVA peptide formulated with L-pampo & TRADE; promoted DC migration into dLNs and increased activation markers and specific DC subsets within dLNs. In addition, vaccines admixed with L-pampo & TRADE; promoted antigen-specific T-cell responses and anti-tumor efficacy. Moreover, the combination of L-pampo & TRADE; with an immune checkpoint inhibitor synergistically improved the anti-tumor effect. This study suggests that L-pampo & TRADE; can be a potent cancer vaccine adjuvant and a suitable candidate for combination immunotherapy.
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关键词
cancer vaccine, TLR agonist, dendritic cell (DC), draining lymph node, anti-tumor efficacy, immune checkpoint inhibitor, combination immunotherapy
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