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The extraordinary and unexpected success of cellular immunotherapy using genetically engineered T-cells to express a chimeric antigen receptor (CAR) targeting CD19, in the treatment of refractory or relapsing B-hematological malignancies, has provided a real therapeutic hope. Indeed, remission rates reach more than 80 % in patients at a stage, without any other possibilities of treatment, notably in the child's acute lymphoblastic leukemia. These results, initially resulting from academic research, led to Food and Drug accreditation for market access of two innovative autologous therapy drugs, Kimryah® and Yescarta®. Based on the impressive clinical results, mainly so far in hematological malignancies (LAL, MM, LBDGC, etc.), the development of several types of cells expressing a CAR receptor suggests a wide range of future applications, particularly in the field of solid tumors. However, while the development of CAR-T cells now appears to be in the hands of private pharmaceuticals companies, the logistical constraints, the cryopreservation and the very high cost of these personalized medicines may ultimately limit their use. The development of academic productions by CAR-T cells could bypass some of these disadvantages. The strong innovation capacity of healthcare institutions associated with research units allows them to identify the ideal tumor target and efficient performing cells. Thus, authorized production platforms could allow for shorter administration times and reasonable production costs for national health systems. The aim of this workshop is to identify the requirements for the academic production of CAR-T cells, while respecting the research standards useful to establish proof of concept, but also at the preclinical development stage, leading in fine to the manufacture, through an authorized pharmaceutical establishment, of the innovative therapy drug, and in accordance with Good Manufacturing Practice (GMP). The ultimate goal is to make these innovative and high-performance medicines available to as many patients as possible.

The extraordinary and unexpected success of cellular immunotherapy using genetically engineered T-cells to express a chimeric antigen receptor (CAR) targeting CD19, in the treatment of refractory or relapsing B-hematological malignancies, has provided a real therapeutic hope. Indeed, remission rates reach more than 80 % in patients at a stage, without any other possibilities of treatment, notably in the child's acute lymphoblastic leukemia. These results, initially resulting from academic research, led to Food and Drug accreditation for market access of two innovative autologous therapy drugs, Kimryah® and Yescarta®. Based on the impressive clinical results, mainly so far in hematological malignancies (LAL, MM, LBDGC, etc.), the development of several types of cells expressing a CAR receptor suggests a wide range of future applications, particularly in the field of solid tumors. However, while the development of CAR-T cells now appears to be in the hands of private pharmaceuticals companies, the logistical constraints, the cryopreservation and the very high cost of these personalized medicines may ultimately limit their use. The development of academic productions by CAR-T cells could bypass some of these disadvantages. The strong innovation capacity of healthcare institutions associated with research units allows them to identify the ideal tumor target and efficient performing cells. Thus, authorized production platforms could allow for shorter administration times and reasonable production costs for national health systems. The aim of this workshop is to identify the requirements for the academic production of CAR-T cells, while respecting the research standards useful to establish proof of concept, but also at the preclinical development stage, leading in fine to the manufacture, through an authorized pharmaceutical establishment, of the innovative therapy drug, and in accordance with Good Manufacturing Practice (GMP). The ultimate goal is to make these innovative and high-performance medicines available to as many patients as possible.

Les médicaments de thérapie innovante (MTI) sont considérés comme de potentielles innovations de rupture pouvant révolutionner la prise en charge des patients. Ils suscitent un très fort enthousiasme dans la communauté scientifique. Les investissements financiers florissent dans ce domaine. Néanmoins, il n’existe sur le marché actuellement qu’une poignée de MTI. L’hypothèse avancée ici, est que le statut de médicament octroyé aux MTI entraîne une réglementation trop stricte autour de ces produits et, est un frein à leur développement. Ainsi, une comparaison des bonnes pratiques de fabrication (BPF) spécifiques des MTI et des bonnes pratiques « tissus – cellules » (BPTC) adaptées aux produits de thérapie cellulaire (PTC), a été effectuée sur un plan sécuritaire et économique. La comparaison des risques analysés de contamination d’une production de MTI et de PTC autologues, ou réalisés à partir d’un donneur pour un patient, selon les BPF et les BPTC, montre une criticité du risque diminuée selon les BPF. Néanmoins, la production de PTC selon les BPTC est déjà considérée comme très sécurisée avec un risque de contamination en cours de production estimé à moins de 1%. La comparaison des coûts de production de cellules souches hématopoïétiques, selon les BPF et les BPTC, montre un surcoût non négligeable (x 2,1) apporté par le statut de médicament. De plus, le développement de ces traitements selon les BPF dans des laboratoires académiques, pourtant plus économique, est limité. Afin d’améliorer l’accès aux thérapies innovantes, au vu des risques de contamination qui ne sont pas si différents, pour un MTI autologue ou réalisé à partir d’un donneur pour un patient, le retour à un statut intermédiaire particulier « PTC innovant », pour lequel les bonnes pratiques seraient adaptées entre les BPF et les BPTC, pourrait être une solution à envisager.