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.

Keywords: Antigen targeting; C-type lectins; Dendritic cells; Immunotherapy; Vaccination.

Figure 1

DC‐based targeting approaches leading to immunity or tolerance. Antigens can be delivered to DC in multiple ways as illustrated here. Antigens can be chemically or genetically conjugated to DC‐specific antibodies expressed on the surface of DC subsets, see Tables 1 and 2 for an overview on potential target receptors. Alternatively, glycosylated antigens can bind to and be taken up by C‐type lectin receptors which is a less specific targeting approach as these receptors can bind multiple sugar moieties. The development of nanocarriers, such as lipid‐based nanoparticles (LNPs), coated with either ligands or antibodies against DC‐specific receptors allows the encapsulation of antigens together with adjuvant for efficient delivery and routing inside the cells. The optimal formulation and delivery routes for nanovaccines need to be studied in the future to optimize DC‐based therapy to induce either tolerance (in the absence of adjuvants) or immunity (in the presence of adjuvants) for the treatment of autoimmunity or infectious diseases as well as cancer. Created with Biorender.com.