Abstract
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The area of therapeutic stem cell research has long been developed in France, and teams are launching clinical trials in rare genetic disorders and neurodegenerative diseases with the objective of producing treatments by the year 2020. The first French clinical trial using embryonic stem cells (ESC) started in 2014 and was dedicated to patients suffering from serious heart failure. In this ongoing, phase I clinical trial, human embryonic stem cell (hESC)–derived cardiac progenitors are incorporated into a biocompatible fibrin gel patch and delivered to the infarcted part of the heart. Retinitis pigmentosa also proved to be an interesting target for cell therapy; the tolerance to an hESC-derived retinal pigmented epithelium cell transplantation is currently being evaluated in a phase I clinical trial. French research is also extremely active in the field of inducible pluripotent stem cells (iPS). One of the main objectives in that domain is to set up a national haplobank to produce cell lines that are to be broadly available for manufacturing cell therapies that match the widest possible number of recipients.
French research has long been strongly committed to the field of gene therapy. Starting with the first gene therapy treatment for X-linked severe combined immunodeficiency (X-SCID), with initial success but also with drawbacks, vectors were improved to safely deliver genes into the patient cells. This helped achieve long-term correction in patients, including T-cell recovery and infection clearance, without any adverse events. In parallel, the pioneer development of lentiviral vectors helped improve hematopoietic stem cell gene therapy. The first phase I/II clinical trial concerned a severe neurodegenerative disease, X-linked adrenoleukodystrophy (ALD), and was followed by hemoglobinopathies and Wiskott–Aldrich syndrome. Lentivectors were also developed for in situ cerebral delivery, and the first phase I/II clinical study for Parkinson's disease was performed, demonstrating tolerance in patients with improvements in motor behavior. Other applications for the central nervous system (CNS) include in situ gene delivery with AAV vectors, particularly for lysosomal storage diseases like San Filippo disease (MPS 3) or metachromatic leukodystrophy (MLD). Major progress was also made in the field of blindness, with injections of AAV vectors helping to cure genetic forms of retinopathies, or preclinical programs reproducing the sensation of sight by inserting light-reactive molecules into optical nerve cells.
Alongside these applications in rare diseases, clinical studies in cancer are currently being developed, with researchers trying to introduce genes that will directly kill the cancer cells with oncolytic vectors or develop immunotherapy with CAR-T cells. In addition, a phase I clinical trial showing safety, feasibility, and trends in efficacy for pancreatic cancer treatment is currently entering phase II. Finally, gene editing technology has been a major step forward in the field of genetic modification and opens future promising avenues for cell and gene therapy applications.
These are not exhaustive examples, and at every step of this adventure, platforms for cell engineering and vector production have been instrumental. Such encouraging results in preclinical research and clinical trials have been possible thanks to the strong support of the national community and French academic institutions, the determination and commitment of patient associations, and the enthusiasm of hundreds of French scientists who dedicate their efforts every day to bringing these emerging and promising technologies to the patients.