Description du projet
Vers des produits pharmaceutiques plus sûrs
Les produits pharmaceutiques, notamment les anticorps, les protéines et les nanotechnologies thérapeutiques, entraînent parfois des pathologies graves qui peuvent s’avérer mortelles, connues sous le nom de réactions d’hypersensibilité (RH). Celles-ci sont provoquées par une réaction allergique réelle en raison de la libération d’IgE ou par une affection pseudoallergique déclenchée par l’activation non spécifique du système du complément. Ce dernier déclenche une importante réponse inflammatoire aiguë associée à la libération de cytokines, d’anaphylatoxines et de complexes destructeurs de cellules. Le projet immunoassays, financé par l’UE, propose de développer et d’évaluer des biomarqueurs prometteurs capables de distinguer entre différents types de RH. Ces biomarqueurs pourraient servir à l’évaluation de la sécurité de nouveaux produits pharmaceutiques.
Objectif
Infusion reactions (IRs) are complex, immune-mediated side effects, also known as hypersensitivity reactions (HSRs), that can occur upon intravenous infusion of pharmaceuticals, leading to severe and sometimes life-threatening conditions in patients. Those reactions may arise from a real allergy which is immune globulin class E (IgE) mediated or a “pseudoallergy”. The latter involves no IgEs and may arise because of activation of the complement (C) system called C activation-related pseudoallergy (CARPA). The complement (C-) system is part of the immune system called the innate immune system that is not adaptable and responds to foreign challenges in a non-specific manner. When stimulated proteases of the complement system cleave other C proteins and initiate an amplifying cascade of further cleavages. The end-result of this activation cascade is a massive acute inflammatory response caused by the release of cytokines, anaphylatoxins and the cell-killing membrane attack complex (MAC). Products triggering severe adverse events can include both traditional small molecules but also biologics such as therapeutic antibodies (Abs), fusion proteins, etc. and novel formulations using liposomes or nanotechnology. Regulatory guidance on the assessment of C-mediated infusion hypersensitivity has been published recently for the case of generic liposome production. Hemocompatibility (blood safety) testing for medical devices is requested by EMA and FDA since many years. However, regarding the potential of new pharmaceuticals causing allergies and/or CARPA remains a significant challenge for the industry during nonclinical development as no established safety biomarker nor meaningful, validated animal models are available up to date. During the project “IMMUNOASSAYS” Dr Fülöp proposes the development and quantitative evaluation of three promising specific safety biomarkers via ELISA technology.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF-EF-SE - Society and Enterprise panelCoordinateur
53359 Rheinbach
Allemagne
L’entreprise s’est définie comme une PME (petite et moyenne entreprise) au moment de la signature de la convention de subvention.