Descrizione del progetto
Verso prodotti farmaceutici più sicuri
I prodotti farmaceutici, compresi gli anticorpi terapeutici, le proteine e le formulazioni di nanotecnologia, conducono talvolta a condizioni gravi e potenzialmente letali conosciute come reazioni di ipersensibilità (HR, Hypersensitivity Reactions). Esse emergono a causa di una reale reazione allergica dovuta al rilascio di immunoglobulina o una condizione pseudoallergica innescata dall’attivazione non specifica del sistema del complemento. Quest’ultimo attiva una risposta infiammatoria massiccia e acuta associata al rilascio di citochine, anafilatossine e complessi che uccidono le cellule. Il progetto immunoassays, finanziato dall’UE, propone di sviluppare e valutare biomarcatori promettenti in grado di discriminare i diversi tipi di HR. Tali biomarcatori potrebbero essere impiegati per la valutazione della sicurezza di questi nuovi prodotti farmaceutici.
Obiettivo
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.
Campo scientifico
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Meccanismo di finanziamento
MSCA-IF-EF-SE - Society and Enterprise panelCoordinatore
53359 Rheinbach
Germania
L’organizzazione si è definita una PMI (piccola e media impresa) al momento della firma dell’accordo di sovvenzione.