The Renaissance of Gene and Cell Therapy: Florence 2016

Gene therapy and cell therapy have been inexorably intertwined as fields of research and clinical care since their inceptions. Studies of hematopoiesis and globin gene regulation were both predecessors of, and platforms for, the earliest ex vivo gene transfer. Limitations of the efficiency and safety of first-generation vectors and of the techniques for isolating and identifying stem cells led to a period of setbacks, slower progress, and declining investment in the late 1990s and early 2000s.

In recent years, however, scientific, technological, and clinical advances have occurred more rapidly. Technological breakthroughs have enabled reprogramming of differentiated cells, precise and efficient editing of the genome, and safe and effective reversal of clinical symptoms in patients with genetic diseases treated with new generations of gene transfer vectors. Not surprisingly, transduction of hematopoietic stem cells has been the leading platform for these advances. Clinical efficacy has been reported in numerous monogenic disorders, including X-linked severe combined immunodeficiency, SCID due to adenosine deaminase deficiency, chronic granulomatous disease, metachromatic leukodystrophy, Wiskott–Aldrich syndrome, beta-thalassemia, and others. In related work, lentivirus transduction and gene editing of lymphocytes have made remarkable clinical impacts in chimeric antigen receptor T cell–based immunotherapy for cancer. Meanwhile, in vivo gene therapy with rAAV has demonstrated success in lipoprotein lipase deficiency, Leber congenital amaurosis, hemophilia B and A, and a number of others. This array of clinical successes has spurred a period of renewed investment by research funding agencies and by industry. The fields of gene and cell therapy are clearly booming and attracting a new generation of promising young scientists.

The 2016 Joint Congress of the European Society of Gene and Cell Therapy, the International Society for Stem Cell Research, and the Italian Association of Cell Biology and Differentiation provide the occasion to celebrate and enhance further this modern “renaissance” of gene and cell therapy. The beautiful setting of Florence serves as a fitting backdrop for this flowering of scientific and clinical discovery. The joint nature of the congress also calls to mind the convergence of fields that was the hallmark of renaissance men and women.

In this context, we as the editors of Human Gene Therapy welcome the opportunity to partner with the editors of Stem Cells and Development in this unique conjoined special issue of the two journals. We are also pleased to welcome Luigi Naldini, a true pioneer of human gene and cell therapy, as Guest Editor for both of these special issues.

These issues contain a number of focused mini reviews on critical topics, authored by international authorities who are themselves immersed in cutting-edge discovery. A number of relevant, high-impact original research papers are also included.

The Human Gene Therapy mini reviews highlight various types of stem and progenitor cells that have been used successfully as platforms for gene and cell therapy, including hematopoietic stem cells, endothelial progenitor cells, T cells, neural stems, induced pluripotent stem (iPS) cells, and urine-derived stem cells. The mini reviews also reflect the tremendous progress in combined gene and cell therapy for a variety of diseases, including a range of genetic diseases, cancer, and lung injury. We are also fortunate to include high-impact original research papers in the field, including proof-of-concept and preclinical studies using combined gene and cell therapy for genetic retinal disease, lysosomal storage disease, and primary hematologic disease. We are confident that this array will resonate well with the activities of the societies and of the Congress itself.

The Stem Cells and Development issue includes, of course, content from Italy, but also reflects the internationality of the congress with contributions from Australia, the United States, and Germany, among others. There is a rich diversity of therapeutic targets including hematological disorders, but also muscular dystrophies, liver disease, and novel cancer therapeutic modalities. It is of interest that even when we first discussed this combined issue project, a deluge of iPS-based papers was anticipated. By far the preponderance are still hematopoietic and then mesenchymal stem cell–based contributions. The exciting broadening of scope of stem cell use into more advanced developmental models, pharmacoscreening, and MiRnome-based prognosis of disease validates our belief in the importance of pursuing multiple avenues of research to achieve clinical goals using cellular therapeutics and development. The Renaissance flourished in 15th-century Florence and elsewhere as a combination of interests in the humanities and the biological sciences, as artistic and medical breakthroughs were achieved shoulder to shoulder. Such developments were achieved with humility to understand achievements of the past, a recognition of the limitations of the present, but with a fierce drive to improve the future. We look forward to sharing our discoveries and visions, and a new era of advanced healthcare.