Highlights of 8th Biennial Congress of the Spanish Society of Gene and Cell Therapy

The 8th Biennial Congress of the Spanish Society of Gene and Cell Therapy (SETGyC) was held from November 4th to 6th in San Sebastian. In the spectacular Kursaal Congress Center facing the surfer's Zurriola Beach, more than 250 attendees enjoyed the talks of 62 invited speakers, 50 selected oral presentations, and 58 posters. Six educational sessions covered a variety of hot topics such as cell and vector GMP manufacturing, regulatory issues, high-throughput single-cell analysis, disease modeling with iPS cells, and new technological developments on systems biology and gene-editing tools. The round tables after each session revealed especial interest on solving limitations of iPS cells and CRISPR-Cas9, and on how to reimburse the high cost of gene and cell therapy products on our open-access public health system. Fulvio Mavilio (Genethon, Evry, France) and Natalie Cartier (University of Paris Descartes) gave the inaugural lectures on muscle and brain gene therapy, respectively. The former showed stable expression of a microdistrophin gene (MD1) and a clear clinical improvement in dogs with Duchenne muscular dystrophy upon systemic treatment with adeno-associated virus (AAV) 2/8-canineMD1 vector. The latter showed that alpha-secretase-derived amiloid precursor protein (APPs alpha) vectored in AAV9 and injected in the hippocampus could rescue cognitive defects in a mouse model of Alzheimer's disease. Alessandro Aiuti (San Raffaele Hospital, Milan, Italy) presented the results on 51 patients affected by adenosine deaminase deficiency, Wiskott–Aldrich, or metachromatic leukodystrophy, which had been treated since 2000 with ex vivo-transduced hematopoietic stem cells, with a remarkably safe long-term correction. In the fantastic closing lecture imparted by Hans Schöler, we learned about the complexity and the factors involved in mammalian cells' pluripotency.

These and other clear examples of clinical benefit in immunodeficiencies, retinopathies, and hemophilia B have contributed to the excitement in the field, which was also evident in the meeting. Gloria Gonzalez-Aseguinolaza (CIMA, Pamplona, Spain) presented results of a phase I trial in eight acute intermittent porphyria patients treated with an AAV5 carrying the porphobilinogen deaminase gene, where liver transduction led to clinical improvement. Juan Bueren (CIEMAT, Madrid, Spain) showed the safe long-term engraftment of hematopoietic stem cells corrected with a lentiviral vector carrying the Fanconi anemia A gene. The phase I/II trial is now ready to start. Another much-awaited forthcoming trial in mucopolysaccharidosis III was presented by Fatima Bosch (Autonomous University of Bellaterra, Barcelona, Spain) supported by long-term efficacy and safety data on mice and dogs using an AAV9-sulfaminase vector. Another mucopolysaccharidosis, the type VII, was also successfully treated in mice with an AAVrh10 vector expressing b-glucuronidase as presented by Assumpsió Bosch (Autonomous University of Barcelona).

The protagonist role of lentiviral vectors for in vitro gene transfer and AAV for in vivo applications was clear. Integration-defective lentiviral vectors avoid genotoxicity but dilute upon cell division. Insertion of episomal replication elements in the lentiviral genome to obtain stable transduction of dividing cells was presented by Juan Carlos Ramírez (Vivebiotech, San Sebastian, Spain). Furthermore, nanoparticle-based vectors are also being explored by groups such as Alicia Rodriguez Gascon and Gustavo Puras (University of Basque Country) and Pilar Martin Duque (CIBA, Zaragoza, Spain), among others, with interesting and promising results.

In the field of cancer cell and gene therapy, attention was focused on immunotherapy, in particular on the use of modified T-cell and oncolytic viruses. Alena Gros from the group of Steven Rosenberg (NIH, Bethesda, MD) was invited to present how tumor mutation-specific T-cells can be isolated from tumors and, most importantly, from peripheral blood of patients. Sonia Guedan from the group of Carl June (UPenn, Philadelphia, PA) showed the potential of CAR T-cells to treat solid tumors, in particular when combined with oncolytic viruses. Ramon Alemany (ICO-IDIBELL, Barcelona, Spain) presented oncolytic adenoviruses modified to target tumors and encouraging efficacy results in neuroblastoma children and in dogs on the use of such viruses loaded on mesenchymal stem cells. The immunostimulatory potential of oncolytic adenoviruses armed with transmembrane IL12 was presented by Ruben Hernandez-Alcoceba (CIMA, Pamplona, Spain). Joan Seoane presented the identification and characterization of glioblastoma initiating cells that led him to discover that the leukemia inhibitory factor mediates immune suppression in this type of tumors and represents an excellent immunotherapeutic target. The therapeutic potential of combinations of immune-checkpoint inhibitors and activators was presented by Ignacio Melero (CIMA, Pamplona, Spain).

In the area of modeling diseases with patient-derived iPS cells, Pablo Menendez (IJC, Barcelona, Spain) showed results on coenzyme Q deficiency, Angel Raya (Center of Regenerative Medicine, Barcelona, Spain) on mucopolysaccharidosis III, and Clara Soria (University of Oviedo) on progeria. The use of gene-editing tools to correct the genetic defect on the iPS cells derived from such patients and the differentiation of the repaired iPS cells to provide differentiated and transplantable cells is an area of huge potential. Examples of this process were presented by Daniel Bachiller (FSIB, Bunyola, Spain) in cystic fibrosis and Jose Carlos Segovia (CIEMAT, Madrid, Spain) in pyruvate kinase deficiency. Fascinating advances in the field of imaging were presented by Cesar Nombela-Arrieta (University of Zürich) and Francisca Mulero (CNIO, Madrid, Spain) to monitor different physiological pathological conditions with a very high sensitivity.

In the cell therapy field, highly promising clinical trial results based on the use of mesenchymal stromal cells were presented by Salvador Martinez (University of Murcia), Consuelo del Cañizo (Salamanca University Hospital), and Damian Garcia Olmo, the latter with a cellular product steadily approaching market approval by EMA. More basic scientific advances increasing our understanding of stem cell biology were also beautifully represented in talks by Simon Mendez-Ferrer (Cambridge Stem Cell Institute), Pura Muñoz-Canoves (University Pompeu Fabra), Isabel Fariñas (University of Valencia), and Hans Schöler (Max Planck Institute, Münster, Germany), among many others. Finally, this year's SETGyC–University Francisco de Vitoria prizes were given to the best oral presentations by Pedro Perdigao (University of Lisbon) and Araika Gutierrez-Rivera (Biodonostia HRI, San Sebastian, Spain) and to the best posters by Sandra Motas (Autonomous University of Barcelona) and Damia Romero-Moya (IJC, Barcelona, Spain).

These are only a few highlights extracted out of the multiple presentations given, and authors apologize to speakers not mentioned here. In summary, the congress in San Sebastian was excellently organized and it reflected an outstanding level of translational science despite the scarce funding devoted to gene and cell therapy in Spain. The meeting was also an opportunity to reinforce the collaboration of the Spanish gene and cell therapists among them and with colleagues who joined the congress from other countries. The assembly of society members decided to elect Ramon Alemany as new president of the society, in substitution of Javier Garcia-Sancho, and Angel Raya as vice president. As a venue for the next meeting in 2017, the city of Palma de Mallorca was preselected.

We want to finish this brief report expressing our gratitude to the organizers, especially Ander Izeta and Gaelle Jamar; the sponsors, especially Becton Dickinson, TerCel, Celgene, Ciberer, Ciberned, Eurofancolen, Praxis, uniQure, VCN Biosciences, and Vivebiotech; and to all the participants, and inviting you to join us in Palma de Mallorca in 2017.