Immune modulation by genetic modification of dendritic cells with lentiviral vectors

Abstract

Our work over the past eight years has focused on the use of HIV-1 lentiviral vectors (lentivectors) for the genetic modification of dendritic cells (DCs) to control their functions in immune modulation. DCs are key professional antigen presenting cells which regulate the activity of most effector immune cells, including T, B and NK cells. Their genetic modification provides the means for the development of targeted therapies towards cancer and autoimmune disease. We have been modulating with lentivectors the activity of intracellular signalling pathways and co-stimulation during antigen presentation to T cells, to fine-tune the type and strength of the immune response. In the course of our research, we have found unexpected results such as the surprising immunosuppressive role of anti-viral signalling pathways, and the close link between negative co-stimulation in the immunological synapse and T cell receptor trafficking. Here we review our major findings and put them into context with other published work.

Keywords: CA; Cancer; Costimulation; DC; Dendritic cell; ERK; IRF; JNK; MA; MAPK; MDSC; MLV; NC; NF-κB; OVA; PD-1; PD-L1; RRE; T cell receptor; T helper; TAA; TCR; TLR; Th; Treg; WPRE; X-SCID; X-linked severe combined immunodeficiency; c-jun kinase; capsid; central DNA flap; cppt; dendritic cell; extracellular signal-regulated kinase; interferon regulatory factor; matrix; mitogen activated protein kinase; mouse leukaemia virus; myeloid-derived suppressor cell; nuclear factor kappa-light-chain-enhancer of activated B cells; nucleocapsid; ovalbumin; pMHC; peptide–MHC complex; regulatory T cell; rev response element; toll-like receptor; tumour associated antigen; woodchuck post-transcriptional response element.