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Development of new immunoassays for the diagnosis and prediction of drug-related complement pathology

Project description

Towards safer pharmaceuticals

Pharmaceuticals, including therapeutic antibodies, proteins and nanotechnology formulations, sometimes lead to severe and life-threatening conditions known as hypersensitivity reactions (HR). These emerge either due to a real allergic reaction driven by the release of IgE or because of a pseudoallergic condition triggered by the non-specific activation of the complement system. The latter triggers a massive acute inflammatory response associated with the release of cytokines, anaphylatoxins and cell-killing complexes. The EU-funded IMMUNOASSAYS project proposes to develop and evaluate promising biomarkers capable of discriminating between the different types of HR. These biomarkers could be employed for the safety assessment of new pharmaceuticals.

Objective

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.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-SE - Society and Enterprise panel

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

TECODEVELOPMENT GMBH
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 174 806,40
Address
MARIE-CURIE-STR. 1
53359 Rheinbach
Germany

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SME

The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.

Yes
Region
Nordrhein-Westfalen Köln Rhein-Sieg-Kreis
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 174 806,40
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