Search

Les decouvertes de cibles therapeutiques et d'outils diagnostiques nouveaux sont aujourd'hui le fruit du developpement considerable de la biologie cellulaire et moleculaire et des biotechnologies. Apres le sequencage du genome humain, la pertinence des donnees obtenues par les techniques a haut debit, notamment celles issues de la genomique et de la proteomique, depend en premier lieu de l'assurance-qualite et de la tracabilite du materiel biologique a partir duquel sont effectuees les recherches, ainsi que des annotations qui qualifient les echantillons. Les Centres de Ressources Biologiques, qui incluent les biobanques, les cryobanques et les tumorotheques sont donc des infrastructures essentielles pour la decouverte d'outils innovants pour la prevention, le diagnostic et le traitement des maladies, et la mise au point de nouveaux medicaments. La constitution d'un reseau de Centres de Ressources Biologiques Humains sur des bases ethiques et juridiques harmonisees constitue aujourd'hui un enjeu majeur pour le developpement de la recherche medicale en Europe.

Resume Le sujet de la table ronde etant initialement tres vaste, il avait ete convenu avec les participants de le recentrer sur les therapies cellulaires (TC) impliquant des cellules autologues utilisees dans des situations de reconstruction tissulaire, d’immunomodulation et de transduction. La TC autologue concerne aussi bien des pratiques tres innovantes que des produits utilises en routine depuis plusieurs annees. Le cadre reglementaire de la TC est maintenant finalise en France. Ce dernier met en exergue le fait qu’un produit de TC est intrinsequement lie a son procede de preparation. L’objectif de cette table ronde etait de definir les pre-requis indispensables a prendre en compte lors du developpement de therapies impliquant des preparations cellulaires ex vivo et ce, afin de s’assurer de la securite d’emploi de tels produits. Les differentes etapes du developpement d’un produit de therapie cellulaire (PTC) ont ete envisagees : (i) contraintes de production permettant de garantir la qualite du produit ; (ii) developpement non clinique : importance de modeles animaux pertinents pour demontrer la preuve du concept et affiner les specifications du PTC ; (iii) developpement clinique : specificite methodologique du developpement d’un PTC. Les problemes inherents a l’utilisation des produits therapeutiques annexes (PTA) au cours du developpement d’un PTC ont ete souleves. Des mesures ont ete envisagees pour qu’a terme l’approvisionnement et la qualite d’un PTA ne constituent pas des facteurs limitants pour le developpement de la TC en France. Enfin, une information des professionnels de sante et des industriels concernant la biovigilance s’est averee necessaire.

The topic of the round table being very broad, it was agreed with the participants that the discussion should be focused on autologous cell therapy (CT) used in tissue repair, immunomodulation or gene transduction. Autologous CT is actually comprised of both very innovative procedures as well as of products used in routine clinical practice. In France, the regulatory framework for CT has now been finalised, underlining the fact that a CT product (CTP) is intrinsically linked to the process used in its preparation. The objective of this round table was to define the essential prerequisites for the development of therapies involving ex vivo cell preparations and, more specifically, to address the issues associated with patient safety during the course of product development. The different stages of CTP development were considered: (i) requirements for CTP manufacturing in order to guarantee product quality; (ii) nonclinical development, and selection of appropriate animal models to provide the proof of the concept and support the definition of CTP specifications; and (iii) clinical development and methodological specificities of CTP development. The specific problems associated with the use of ancillary therapeutic products (ATPs) during the development of a CTP were discussed. Actions were proposed to ensure long-term supply of ATPs, which may be a significant bottleneck for the development of CT in France. Eventually, new regulatory provisions will come into force in the area of biovigilance, and it was deemed necessary for healthcare and industry professionals to be appropriately involved in the implementation phase.

Continuing advances in life sciences and medical research are the result of the remarkable achievements of cell and molecular biology. In the post-sequencing era, the quality of the huge amount of data continuously generated by biotechnology, i.e. genomics, proteomics and high-throughput screening, depends on the quality assurance and the traceability of the original biological materials, including the annotations linked to these materials. Thus, biological resource centres are key infrastructures supporting biotechnology, bioprocessing and the development of new approaches in the prevention, diagnosis and treatment of diseases.

CPT-11 is a water-soluble analog of camptothecin synthesized by Yakult Honsha Co. Ltd (Japan). CPT-11 and its main metabolite SN-38 are active against a variety of human cancer cell lines, even in resistant cell lines [1], as well as in murine tumor models [2]. Their mechanism of action is presumed to be through inhibition of Topolsomerase I. A previous Japanese Phase I study of CPT-11 established the MDT at 250 mg/m2 as a single dose. The dose limiting toxicity was leukopenia with mild anemia and thrombocytopenia [3]. The recommended dose for Phase II trials was 200 mg/m2 every 3 weeks. Phase II trials started in Japan with different therapeutic schedules, and showed interesting response rates in lung cancers and others tumors including colorectal, gastric, cervical, ovarian [4,5] and hematological malignancies [6].