Descripción del proyecto
Hacia unos productos farmacéuticos más seguros
Los productos farmacéuticos, incluidos los anticuerpos terapéuticos, las proteínas y las formulaciones nanotecnológicas, a veces conducen a trastornos potencialmente mortales conocidos como reacciones de hipersensibilidad. Estas surgen debido a una reacción alérgica real provocada por la liberación de inmunoglobulina E o a una pseudoalergia desencadenada por una activación no específica del sistema complemento. Este desencadena una respuesta inflamatoria aguda masiva asociada con la liberación de citoquinas, anafilatoxinas y complejos citolíticos. El proyecto financiado con fondos europeos immunoassays propone desarrollar y evaluar biomarcadores prometedores capaces de distinguir entre tipos distintos de reacciones de hipersensibilidad. Estos biomarcadores podrían utilizarse para la evaluación de la seguridad de los productos farmacéuticos nuevos.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF-EF-SE - Society and Enterprise panelCoordinador
53359 Rheinbach
Alemania
Organización definida por ella misma como pequeña y mediana empresa (pyme) en el momento de la firma del acuerdo de subvención.