Receptor-Mediated Delivery of Antigens to Dendritic Cells:  Anticancer Applications

Abstract

Recently, there has been a surge of interest in the use of ex vivo antigen-pulsed dendritic cells (DCs) in the immunotherapy for cancer. DCs are powerful adjuvants with the ability to prime naive CD4+ and CD8+ T cells. As antigen sources, various preparations, including peptides, proteins, crude tumor lysates, and DCs transfected or transformed with various viruses, have been used. These procedures that involve the isolation of patient DCs and reintroduction after in vitro manipulation are time-consuming and expensive. The DC populations used frequently in ex vivo clinical studies are IL-4 and GM-CSF cultured DCs that may not represent the in vivo DC populations. An attractive method of targeting in vivo DCs is to utilize various ligands or antibodies that bind discrete populations of DCs. These cell surface receptors will direct the antigen to different antigen processing pathways depending on the targeted receptor to induce cytotoxic T cell or T helper responses. This review will discuss the various approaches and receptors that have been used for antigen targeting that may eventually be translated to alternative DC-based immunotherapies.

Targeting of DEC-205 on human dendritic cells results in efficient MHC class II–restricted antigen presentation

“…Although in several vaccination trials Ag was formulated with adjuvant, which directly or indirectly mediates uptake by DCs and their maturation, 45 receptor targeting of DCs with specific constructs was not yet performed in humans. Experiments in mice and in vitro experiments with human DCs showed first promising results, indicating that in vivo targeting of DCs may be applicable as a therapeutic modality in cancer immunotherapy.…”

CD11c provides an effective immunotarget for the generation of both CD4 and CD8 T cell responses

“…A range of approaches is being considered for targeting, including Ab [3][4][5] and synthetic nanoparticles [6]. Administration of Ag conjugated to ligands or Ab that bind specific DC receptors has been extensively investigated as a means of targeting directly to DC in vivo and thereby enhance uptake and presentation [7]. The immunological outcome of such targeting is influenced by the distribution of the targeted receptor among DC subsets, the specific receptor targeted and the presence or absence of coadministered adjuvant [8][9][10][11][12][13][14].…”

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

“…One crucial class of such receptors is the C-type lectin, which contains carbohydrate-binding motifs that recognize a wide array of sugar-associated ligands [1,2]. C-type lectins such as the mannose receptor (MR, CD206), DC-SIGN (CD209), Dectin-1 and langerin have a high affinity for mannosylated antigens [2,3].…”