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

SIMPLE SUMMARY: Toll-like receptor (TLR) agonists induce strong immune responses, which are used as an effective adjuvant system for vaccine development. L-pampo™ 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™. We demonstrate that L-pampo™ directly stimulates the maturation and function of dendritic cells, which are essential antigen-presenting cells. Additionally, the vaccine formulated with L-pampo™ 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™ with immune checkpoint inhibitors induces a synergistic anti-tumor effect, indicating that L-pampo™ can be a powerful cancer vaccine adjuvant and a potent partner for combination immunotherapy. ABSTRACT: TLR agonists have emerged as an efficient cancer vaccine adjuvant system that induces robust immune responses. L-pampo™, 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™ 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™ 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™. We found that L-pampo™ directly enhanced the maturation and cytokine production of DCs and, consequently, T-cell proliferation. OVA or OVA peptide formulated with L-pampo™ promoted DC migration into dLNs and increased activation markers and specific DC subsets within dLNs. In addition, vaccines admixed with L-pampo™ promoted antigen-specific T-cell responses and anti-tumor efficacy. Moreover, the combination of L-pampo™ with an immune checkpoint inhibitor synergistically improved the anti-tumor effect. This study suggests that L-pampo™ can be a potent cancer vaccine adjuvant and a suitable candidate for combination immunotherapy.