Abstract
A successful anti-cancer vaccine construct depends on its ability to induce humoral and cellular immunity against a specific antigen. Targeting receptors of dendritic cells to promote the loading of cancer antigen through an antibody-mediated antigen uptake mechanism is a promising strategy in cancer immunotherapy. Researchers have been targeting different dendritic cell receptors such as Fc receptors (FcR), various C-type lectin-like receptors such as dendritic and thymic epithelial cell-205 (DEC-205), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), and Dectin-1 to enhance the uptake process and subsequent presentation of antigen to T cells through major histocompatibility complex (MHC) molecules. In this review, we compare different subtypes of dendritic cells, current knowledge on some important receptors of dendritic cells, and recent articles on targeting those receptors for anti-cancer immune responses in mouse models.
Highlights
Checkpoint inhibitors (CTLA-4, PD-1/PD-L1), adoptive cell transfer, monoclonal antibodies and cancer vaccines are among the most popular cancer immunotherapy modalities available so far
Antigen presenting cells (APCs) such as macrophages and dendritic cells express C-type lectin receptors (CLRs) that serve as pattern recognition receptor (PRRs) and bind to pathogen associated molecular patterns (PAMPs) or self-antigen released from dead cells [37]
On the other hand, binding of Fc with an inhibitory receptor triggers the phosphorylation of inhibitorynecrotic motifs (ITIMs), and through downstream signaling inhibits the activation of Src kinases and phospholipase C γ (PLCγ)
Summary
Checkpoint inhibitors (CTLA-4, PD-1/PD-L1), adoptive cell transfer, monoclonal antibodies and cancer vaccines are among the most popular cancer immunotherapy modalities available so far. Antigen is bound with antibody and targeted to a dendritic cell receptor for internalization, processing and presentation (Figure 1). This review highlights the importance of different kinds of dendritic cell receptors crucial for an effective antibody-targeted vaccination approach and the recent findings associated with targeting those receptors. We discuss how these findings may have an impact on our understanding of the receptor binding interaction focusing on DCs. We begin, by reviewing different dendritic cell subsets and their biology, receptors present on different subsets and targeting those receptors through corresponding antibody–antigen conjugation approaches.
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