Antigen targeting to dendritic cells: Still a place in future immunotherapy?

Abstract

The hallmark of DCs is their potent and outstanding capacity to activate naive resting T cells. As such, DCs are the sentinels of the immune system and instrumental for the induction of immune responses. This is one of the reasons, why DCs became the focus of immunotherapeutical strategies to fight infections, cancer, and autoimmunity. Besides the exploration of adoptive DC-therapy for which DCs are generated from monocytes or purified in large numbers from the blood, alternative approaches were developed such as antigen targeting of DCs. The idea behind this strategy is that DCs resident in patients' lymphoid organs or peripheral tissues can be directly loaded with antigens in situ. The proof of principle came from mouse models; subsequent translational studies confirmed the potential of this therapy. The first clinical trials demonstrated feasibility and the induction of T-cell immunity in patients. This review will cover: (i) the historical aspects of antigen targeting, (ii) briefly summarize the biology of DCs and the immunological functions upon which this concept rests, (iii) give an overview on attempts to target DC receptors with antibodies or (glycosylated) ligands, and finally, (iv) discuss the translation of antigen targeting into clinical therapy.

Straight to the point: targeted mRNA-delivery to immune cells for improved vaccine design

“…This opens the possibility to develop vaccines that can elicit stronger humoral (antibody-mediated) responses, cellular immune responses, or a combination of both, according to the pathogen’s nature and the desired immunological outcome. Indeed, this strategy has already been applied successfully to subunit vaccines ( 32 – 34 ). Altogether, DC targeting could potentially not only improve mRNA vaccine efficacy, but also expand the range of pathogens for which they do effectively work, including those that have developed mechanisms to bypass the immune system, which are some of the most challenging to address ( 35 ).…”

“…Interestingly, some CLRs like Dectin-2 (Clec6a) are shown to improve phagocytosis although they do not directly participate in the phenomenon, but likely trigger signaling which in turn catalyzes the engulfment process ( 108 ). In summary, CLRs are considered attractive targets for targeted antigen and mRNA-delivery ( 34 ) due to their broad expression on antigen presenting cells, their selectivity and their role in internalization, antigen processing and immune activation.…”

Recent Findings on Therapeutic Cancer Vaccines: An Updated Review

“…Most of the recent developed cancer vaccines are based on using whole cells like DCs, which affect the function of the cells in the immune system. The importance of DCs in antigen uptake and presentation processes, as well as T cell activations, which are mediated by a wide spectrum of receptors present on DCs' surfaces, including those for antigen uptake, antigen presentation, costimulatory molecules, cytokines receptors, receptors for environmental sensors, cytokine production-related receptors, as well as chemokine receptors, have turned DCs into the most commonplace immune cells used in developing immune cell-based cancer vaccines [12,22,39,49,147,[152][153][154]. To improve the efficacy of DCs in antigen absorption and T cell activation, researchers have started to use stem cells to develop better cell-based cancer vaccines.…”

Mining the Immunopeptidome for Antigenic Peptides in Cancer

“…Post-translationally modified proteins undergo processing through the proteasome, resulting in peptides that bind to MHC-I for endogenous proteins or MHC-II for exogenous proteins [ 26 ]. Dendritic cells (DCs) are antigen-presenting cells (APCs) in cancer that are essential for T and B cell responses via immunopeptides and native protein presentation, respectively [ 27 , 28 ]. PTMs that are restricted to tumor cells have potential as a source of immunopeptides for immunotherapy.…”