Fig. (3).

Targeting intracellular signalling pathways by genetic modification of DC. Gene therapy techniques allow the modification of DC function by introducing specific genes that modify intracellular signalling pathways. These signalling pathways will ultimately modify DC function by either increasing or suppressing their immunogenicity. In the figure, a viral vector carrying the therapeutic genes binds to the cell membrane (receptor recognition) and it fuses directly to the cell membrane leading to the core release. As it is the case of other vectors either based on retroviruses or not, virus-like particles can also be internalised by endocytosis. In the case of lentivectors (and other retrovirus-based vectors), through a process of reverse transcription, the therapeutic genetic information encoded as RNA is copied into a DNA version that is transported to the cell nucleus. Then, the therapeutic DNA genes are incorporated into the host genome, and they will lead to transcription and translation of both TAA and modulators of DC signalling (DC modulators). In this case, activation of ERK, JNK, p38 and NF-κB is depicted. Activation of these pathways will regulate DC maturation phenotype and cytokine secretion, and ultimately will enhance presentation of TAA to specific CD4 and CD8 T cells as shown in Fig. (1).