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

Chumeng Chen,Mohanad Aldarouish,Feng Han,Xiangzhen Liu,Qilong Li,Qijun Qian,Hui Liu

doi:10.1155/2020/3965061

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.

Highlights

The unique characteristics of dendritic cells (DCs) as the most potent antigen-presenting cells (APCs) lead them to be considered as a promising tool for cancer immunotherapy [1]
To detect whether the covalent linking of synthetic peptides with HB100-108 via RR linker could accelerate their acquisition by DCs, cells were incubated with survivin±HB100-108, human epidermal growth factor receptor 2 (Her2)±HB100-108, or carcinoembryonic antigen (CEA)±HB100-108 in culture medium for 1 hour at 37°C
These findings indicate that HB100-108 could play an important role in the acceleration of peptide phagocytosis by immature DCs

Summary

Introduction

The unique characteristics of dendritic cells (DCs) as the most potent antigen-presenting cells (APCs) lead them to be considered as a promising tool for cancer immunotherapy [1]. In the last few years, there has been a growing interest in peptide-, RNA-, and DNA-based DC vaccines as an effective approach for cancer immunotherapy due to its promising results in achieving significance and durable treatment responses with mild adverse events [2, 3]. Peptide-based vaccines provide several advantages in comparison to other types of cancer vaccines. They are synthesized, stable in many storage conditions, and safe, and they could enhance an effective CD4 and CD8 immune response. High mobility group box 1 (HMGB1) is highly conserved protein in mammals that translocates to the nucleus to regulate the gene expression and released during cell injury and inflammation [5]. HMGB1 is composed of two DNAbinding motifs, box A and box B, in addition to C tail

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