Immunity of Lentiviral Vector-Modified Dendritic Cells

Innovative approaches to induce a strong immune response are key to the success of immunotherapy. Dendritic cells (DCs) are professional antigen-presenting cells (APCs) equipped with co-stimulatory, adhesion, and major histocompatibility complex (MHC) molecules needed for initiation and reactivation of the immune response. DCs are able to initiate and stimulate both innate and adaptive immune responses and, by secretion of cytokines, chemokines, and expression of regulatory molecules, to shape the adaptive immune response toward a long-lasting memory immunity. DCs from the peripheral blood of immune-compromised patients, however, often display an immature phenotype with defective functions. This emphasizes the importance and potential of engineering antigen-specific DCs in vitro. A state-of-the-art approach to overcome the prevailing immune dysfunction(s) in patients is to engineer DCs or DC progenitors to generate fully functional DCs for the modification of host immunity. Lentiviral vectors (LVs) are highly efficient gene transfer vehicles for engineering DC functions. Examples of lentiviral vectors encoding immune-modulatory genes and useful functional assays for the analysis of effector immune cell response are described in this chapter.