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. 2020 Jul 14;12(7):663. doi: 10.3390/pharmaceutics12070663

Figure 4.

Figure 4

The rationale for targeted DC vaccine design is build up upon three pillars including the employed targeting antibody, the tumor antigen, and adjuvant(s). Antibody-based shuttle systems directed against specifically expressed endocytic receptors are a potent tool allowing for the delivery of antigens to specialized conventional dendritic cell (cDC) subpopulations. Thereby, the subset intrinsic capability to induce distinct T cell effector molecules would be utilized therapeutically. While targeting antibodies determine the specificity for a distinct cDC subpopulation, the selection of tumor antigens dictates the T cell specificity during vaccination approaches. Depending on the tumor, different antigen classes are available. Finally, the use of adjuvants determines the nature of the induced immune responses, thereby potentially allowing to break tolerance against tumor-derived antigens during peptide presentation on DCs to T cells. The manifold of adjuvant classes and effects enables complex manipulations of DCs. Adjuvants include pathogen sensor agonists stimulating and polarizing DC activity following sensing, direct application of cytokines mobilizing the DC pool or supporting DC activation, or delivery of miRNAs or siRNAs allowing for manipulation of regulatory pathways in DCs. Depending on the desired T cell immune response, the vaccine formulation should incorporate agents from every column. CLEC = C-type lectin receptor; Dendritic cell immuno-receptor 2 = DCIR2; FcγR = Fc gamma receptor; MHC = major histocompatibility complex; DC = d1endritic cell; cDC = conventional dendritic cell; gp100 = glycoprotein 100; Her2/neu = human epidermal growth factor 2; HPV = human papilloma virus; EBV = Epstein-Barr Virus; MAGE = Melanoma Antigen Gene; NY-ESO-1 = New York esophageal squamous cell carcinoma-1; TLR = Toll-like receptor; NLRs = Nucleotide-binding oligomerization domain-like receptors; RLR = RIG-I-like receptor; STING = Stimulator of interferon genes; FLT3 = Fms-like tyrosine kinase 3; FLT3-L = Fms-like tyrosine kinase ligand; IFN = Interferon; miRNA = micro RNA; siRNA = small interfering RNA.