Triggered Immune Response Induced by Antigenic Epitopes Covalently Linked with Immunoadjuvant-Pulsed Dendritic Cells as a Promising Cancer Vaccine

Abstract

The success of peptide-based dendritic cell (DC) cancer vaccines mainly depends on the utilized peptides and selection of an appropriate adjuvant. Herein, we aimed to evoke a broad immune response against multiple epitopes concurrently in the presence of immunoadjuvant. Three synthetic HLA-A∗0201-restricted peptides were separately linked with HMGB1-derived peptide (SAFFLFCSE, denoted as HB100-108) as immunoadjuvant via double arginine (RR) linker and loaded onto human monocyte-derived DCs. Peptide uptake was detected by immunofluorescence microscopy and flow cytometry. The maturation and activation status of pulsed DCs were monitored by detection of the expression of specific markers and released cytokines. The ability of peptide-pulsed DCs to activate allogeneic T cells has been assessed by a degranulation assay and detection of secreted cytokines. The lytic activity of effector T cells against cancer cells in vitro was analyzed by a lactate dehydrogenase (LDH) assay. Results revealed that DCs efficiently take up peptides+HB100-108 and expressed higher levels of surface markers (HLA-ABC, HLA-DR, CD80, CD86, CD83, CD40, and CCR7) and proinflammatory cytokines (IL-6, IFN-γ, TNF-α, and IL-12) than control DCs, free peptide-pulsed DCs, and free HB100-108-pulsed DC groups. Moreover, peptides+HB100-108/pulsed DCs were capable of activating allogeneic T cells and enhance their lytic activity against a pancreatic cancer cell line (PANC-1) in vitro. These findings suggest that antigenic peptides covalently linked with HB100-108/pulsed DCs could be a promising strategy to improve the current DC-based cancer vaccines.

Single‐cell RNA sequencing reveals heterogeneity and differential expression of decidual tissues during the peripartum period

“…A total of 17 149 cells (three samples) before labour onset and 12 082 cells (three samples) after delivery were analysed (Figure 1D). Using the Cell Marker database 19 combined with published literature, 13‐15,20,21 eight cell types were identified (Figure 1E,F), including endothelial cells, decidual stromal cells, extravillous trophoblasts and T cells. In addition, smooth muscle cells were identified by MSC , MYH11 , FOXS1 and ACTA2 .…”

“…Figure 1D). Using the Cell Marker database 19 combined with published literature, [13][14][15]20,21 low PRL expression in decidual stromal cells were found during early pregnancy. 13 In addition to the inconsistent PRL expression in these three subgroups (cluster 2, cluster 6 and cluster 13), GSTA1 and CLDN10 expression differences could be used to distinguish them ( Figure 2K Figure 3C).…”

“…A total of 17 149 cells (three samples) before labour onset and 12 082 cells (three samples) after delivery were analysed (Figure 1D). Using the Cell Marker database 19 combined with published literature, [13][14][15]20,21 As one of the best indicators of decidualization, 23 IGFBP1 can be used to recognize decidual stromal cells in peripartum decidua (Figure 2H). PRL and IL-15 were differentially expressed in decidual stromal cells (Figure 2I,J).…”

Personalized neoantigen viro-immunotherapy platform for triple-negative breast cancer

“…Usually, selected antigens are delivered together with adjuvants to induce a proper immune response. [24][25][26] Use of replicating oncolytic viruses (OV) to deliver antigens into the tumor could offer a tremendous advantage over common adjuvants, as when administered directly into the tumor they can double as both adjuvants and oncolytic agents, resulting in an enhanced overall antitumor effect. We have recently developed a new generation of tumor-targeted replicating vaccinia virus (VV) (VVLΔTKΔN1L) with deletion of the thymidine kinase and N1L genes that enhance safety (selectively targeting tumors with deregulated Ras-EGFR pathways).…”