imSAVAR – Immune Safety Avatar: Nonclinical mimicking of the immune system effects of immunomodulatory therapies

In the imSAVAR project, an interdisciplinary EU consortium is developing innovative model systems to identify side effects of immunomodulating therapeutics on the immune system and to develop new biomarkers for diagnosis and prognosis. Fraunhofer IGB is involved in the development of novel immunocompetent in vitro models based on organ‑on‑chip systems as well as of cell‑based reporter gene assays using receptors of the immune system. Furthermore, they are part of the project management team.

© Fraunhofer IZI
Kick-off meeting of the imSAVAR consortium at Fraunhofer IZI, Leipzig, on December 2, 2019.

In the imSAVAR project, an interdisciplinary EU consortium is developing innovative model systems for the evaluation of immunomodulating therapeutics. The EU project started its six‑year research project on December 1, 2019, and is funded within the public‑private partnership Innovative Medicines Initiative (IMI). Under the scientific leadership of Fraunhofer IZI, Fraunhofer IGB participates in project management and project coordination.

 

Challenges

A first essential step in the development of new active substances is the pre‑clinical evaluation of the efficacy and safety of the therapeutic agent. At present, preclinical evaluation is hardly possible in the development of immunomodulating therapeutics, for example in immune oncology and immune‑mediated diseases, because existing models do not adequately represent the complexity of the immune system and thus individual interactions of the human immune system in the diseased state cannot be reflected.

 

Objectives and project plan

The aim of the EU‑funded project Immune Safety Avatar (imSAVAR) is therefore the improvement of existing and the development of new model systems and their validation as a platform for the non‑clinical assessment of the safety and efficacy of immunomodulatory therapies. This should enable the identification of undesirable side effects of new therapies on the immune system and the development of new biomarkers for diagnosis and prognosis.

In the project, Fraunhofer IGB coordinates the development of novel immunocompetent in vitro models, which are being set up in cooperation with partners from the Universities of Jena, Tübingen and Twente, Fraunhofer IWS and the Leiden University Medical Center (LUMC). The focus here is on microphysiological systems, especially organ‑on‑chip platforms with which immune‑mediated effects and toxicities can be investigated directly in human tissue. The results can thus be directly transferred to humans and animal experiments can be reduced.

In addition to the organ‑on‑chip models, cell‑based reporter gene assays with immune receptors will be developed and established. These new in‑vitro assays are used to assess the efficacy, for example in immunomodulating drug screening, and the safety of new immunotherapies. In addition, corresponding reporter cells are also used in immunocompetent 3D skin models.

 

Impact

The imSAVAR platform will be evaluated through case studies for prioritized therapeutic modalities. This will involve all relevant stakeholders, including patients and regulators.

Project information

Project title

imSAVAR – Immune Safety Avatar: Nonclinical mimicking of the immune system effects of immunomodulatory therapies

 

Project duration

December 2019  – November 2025

 

Project partners

  • Fraunhofer Institute for Cell Therapy and Immunology IZI, Germany (Coordination)
  • BioSci Consulting, Belgium
  • bluebird bio, Inc. United States
  • Boehringer Ingelheim, United States
  • Covance, United Kingdom
  • Dynamic42 GmbH, Germany
  • F. Hoffmann-La Roche Ltd, Switzerland
  • Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Germany
  • Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Germany
  • Fraunhofer Institute for Material and Beam Technology IWS, Germany
  • Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Germany
  • Hannover Medical School (MHH), Germany
  • IT for Translational Medicine S.A. (ITTM), Luxembourg
  • Jena University hospital, Germany
  • JDRF, United States
  • Leiden University Medical Center (LUMC), The Netherlands
  • Leipzig University, Germany
  • Lund University, Sweden
  • Merck KGaA, Germany
  • Merck Sharp & Dohme Corp., United States
  • Novartis AG, Switzerland
  • Medical University of Innsbruck, Austria
  • Paul-Ehrlich-Institut (PEI), Germany
  • Sanofi, France
  • Servier, France
  • T-CURX GmbH, Germany
  • Transgene SA, France
  • University Hospital of Würzburg, Germany
  • University Hospital of Tübingen, Germany
  • University of Luxembourg, Luxembourg
  • University of Oslo, Norway
  • University of Twente, The Netherlands

Funding

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853988. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.