Editorial [Hot Topic:Gene Therapy for Modulating Immune/Inflammatory Responses (Guest Editor: Maria Manunta)]

There has been fluctuating interest in gene therapy since the first therapeutic gene was successful delivered. However, gene therapy still offers substantial potential in modern medicine, as evidenced by clinical realisation of therapeutic gene delivery in those areas in which pharmacological interventions are lacking or failing. The possibilities of therapies are rather broad ranging from inherited disorders to emerging or re-emerging diseases. From this perspective, two factors have played a crucial role: the identification of genes related to biological dysfunction and the development/isolation of new and promising gene delivery systems. Immunology is implicitly linked to gene therapy from many different aspects. Gene therapy can in fact be used to treat immunological/haematological disorders and to manipulate the immune system by enhancing or preventing inflammation and/or the immune response. On the other hand, gene therapy itself can stimulate the immune system either through the delivery vector or the transgene, leading to serious complications. This special focus issue on gene therapy for modulating immune/inflammatory responses is articulated in two main subtopics, describing respectively direct targeting of the immunological precursor/effector and indirect approaches to modify the inflammation/immune response. In the first part of this issue, Imai et al. examine the perspective of natural killer cell gene therapy and provides clues as to how it is possible to genetically modify these effectors by expressing chimeric receptors targeting cancer (specifically leukemic cells). The current status of gene therapy approaches for the treatment of rheumatoid arthritis is discussed by Vervoordeldonket and collaborators, who also point out the safety issues related to the clinical approach. In their review, Von Laer et al. describe the approaches aiming to reconstitute a functional immune system in AIDS patients and provide recent insights into the latest clinical trial. In the second subtopic, Carey et al. focus on the induction and re-establishment of tolerance by targeting B cells. Okada and Butterfield detail the efforts made in tumour vaccinology through manipulation of dendritic cells. In their paper Tschoeke and Oberholzer highlight how our current understanding of dendritic cell biology had provided new tools to modulate acute inflammation. Finally, our group describes strategies used to target endothelial cells in order to induce tolerance or stimulate the immune response and highlights some issues that can affect gene delivery to endothelium. We hope that the publication of comprehensive and critical reviews will provide a significant contribution to our understanding of how gene therapy can be used to modulate the immune response. A personal thank to Andrew George for his precious suggestions, Mark Gumbleton for providing some editorial tips and Saima Ghaffar for her support.