The rationale for developing dendritic cell (DC)-targeted immunotherapies stems from their essential role in immune orchestration. Ex-vivo matured DCs produced from monocytes or myeloid DCs isolated from peripheral blood have been used in the majority of research addressing antigen-targeting to DCs for inducing T cell responses. Plasmacytoid DCs (pDCs) have lately emerged as appealing targets that can be easily separated and stimulated ex vivo. Because of their remarkable capacity to create significant amounts of type-1 interferons in response to signaling via TLR7 or TLR9 intracellular receptors for viral RNA or bacterial DNA, pDCs are known as essential effectors of innate and adaptive immunity. From this study, researchers could describe and define the immune modifying and targeting module of a composite human-specific vaccination platform for active immunotherapy. The warhead (WH) module is made up of a single-chain variable fragment (scFv) and covalently attached CpG-C type oligonucleotides (ODNs). The scFv facilitates selective binding to FcRII/CD32 on APCs as well as the internalization of ODNs, which stimulates TLR9-expressing B cells and pDCs. Furthermore, the scFv in the WH is extended with a five-time heptad repeat (EVSALEK) alpha helix, allowing for the creation of a coiled-coil complex with any immunogen that is likewise extended with a five-time heptad repeat (KVSALKE).
The production of interferon-α, TNF-α, and IL-6 by WH evoke rapid and strong pDC activation. The WH, therefore, makes use of the fundamental immunostimulatory properties of human pDCs and can be a flexible tool for antigen-specific immunization with a range of proteins or peptides.