Reconstructing the immune system with lentiviral vectors

Lentiviral vectors (LVs) developed in the past two decades for research and pre-clinical purposes have entered clinical trials with remarkable safety and efficacy performances. Development and clinical testing of LVs for improvement of human immunity showed major advantages in comparison to other viral vector systems. Robust and persisted transduction efficiency of blood cells with LVs, resulted into a broad range of target cells for immune therapeutic approaches: from hematopoietic stem cells and precursor cells for correction of immune deficiencies, up to effector lymphoid and myeloid cells. T cells engineered for expression of chimeric antigen receptors (CARs) or epitope-specific transgenic T cell receptors (TCRs) are in several cancer immune therapy clinical trials worldwide. Development of engineered dendritic cells is primed for clinical trials for cancer and chronic infections. Technological adaptations for ex vivo cell manipulations are here discussed and presented based on properties and uses of the target cell. For future development of off-shelf immune therapies, direct in vivo administration of lentiviral vectors is warranted and intended. Approaches for lentiviral in vivo targeting to maximize immune therapeutic success are discussed.