Multi-signaling pathway activation by pH responsive manganese particles for enhanced vaccination

Minimalist Nanovaccine with Optimized Amphiphilic Copolymers for Cancer Immunotherapy

“…To mechanically investigate the ability of C-25 to activate DC maturation, transcriptome analysis of BMDCs incubated with C-25 or phosphate buffered saline (PBS) was carried out (Figure 2a). As shown in the ring numeric heatmap, the related genes encoding BMDC maturation related molecules, 15,42 tumor necrosis factors (TNFs) and receptors, interleukins and receptors, as well as chemokines and receptors in C-25-treated DCs were significantly upregulated (Figure 2b). Besides, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis further indicated that C-25 synergically activated BMDCs through multiple signaling pathways, such as the TLR signaling pathway, nuclear factor kappa B (NF-kappa B) signaling pathway, nucleotide oligomerization domain (NOD)-like receptor signaling pathway, cytokine−cytokine receptor interaction, and other related inflammatory pathways (Figure 2c).…”

“…Cancer immunotherapy has become an encouraging strategy to treat or even cure cancer by leveraging patients’ own immune system to attack cancer cells. − Different types of cancer immunotherapies including chimeric antigen receptor T-cell therapy, immune checkpoint blockade therapy, cytokine therapy, together with cancer vaccines have been extensively used in the clinic and have achieved exciting clinical results. − Among them, a cancer vaccine that can stimulate potent tumor-specific immune responses is considered to be a promising strategy to prevent and eradicate cancer. − Despite its promising prospects, the cancer vaccine still faces some critical challenges including insufficient antigen and adjuvant delivery, deficient antigen presentation, and inadequate maturation of antigen-presenting cells (APCs). − For an efficient cancer vaccine, antigens specific to tumors and adjuvants should be successfully delivered into APCs, and subsequently these antigens must be cross-presented to T cells through the major histocompatibility complex class I (MHC-I) antigen-presenting pathway of APCs. , Therefore, there is still a considerable need to develop an efficient delivery carrier for a cancer vaccine …”

Biomineralization-inspired synthesis of autologous cancer vaccines for personalized metallo-immunotherapy

“…Mn 2+ can stimulate the cGAS-STING pathway to promote DC maturation and the secretion of diverse downstream proinflammatory cytokines (e.g., IFN-β). 41 , 42 , 43 We then explored the capacity of OVA@MnP to activate the cGAS-STING pathway via a series of standard characteristic experiments. It has been well documented that cGAS-transfected 293-Dual mSTING reporter cells (ISG-SEAP/KI-[IFN-β]Lucia) can activate STING by secreting Lucia luciferase in place of IFN-β.…”

Nanotechnology‐Empowered Combination Cancer Immunotherapies: Mechanisms, Synergies, and Perspectives

“…Elsewhere, Lv et al developed a novel nanovaccine by loading model antigen ovalbumin (OVA) through forming nanocoordinated polymers by Mn 2þ and 2-methylimidazole. [121] The design effectively activated bone marrow-derived dendritic cells by Mn 2þ , enhancing their maturation, antigen cross-presentation, and innate immune response in the organism. Nanovaccines can induce humoral and cellular immunity responses, generating specific immune memory, and, when combined with anti-PD-1 antibody, provide a comprehensive enhancement of both innate and adaptive immunity.…”