LUMC participates in EU project to develop innovative model systems for the evaluation of immunomodulatory therapeutics

24 December 2019• NEWSITEM

The development of immunomodulatory agents and therapies has received fresh impetus following the latest successes in immuno-oncology. And cancer medicine is not the only area where cell and gene therapies are increasingly taking hold as alternatives or complementary to classic, low-molecular drugs and biologicals.

A significant challenge facing the development of new therapies, however, is and remains their preclinical evaluation in terms of efficacy and safety. The greatest problem here is the complexity of the human immune system. When a person is ill, for example in the case of cancer, autoimmune or inflammatory diseases, the cells of the immune system interact differently to when a person is healthy. While preclinical tests have so far mainly looked at the basic toxicity of a new therapeutic agent in terms of the (healthy) immune system, there is a lack of non-clinical models that accurately capture the individual interactions of the human immune system in the pathogenic state.

Improve existing model systems

The EU consortium imSAVAR (Immune Safety Avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies) is addressing this shortfall by coming up with new ways of examining immunomodulatory therapies. The aim here is to improve existing model systems and develop new ones in order to:

  •          identify adverse side effects of new therapies affecting the immune system,
  •          develop new biomarkers for diagnosing and predicting immune-mediated pharmacology and toxicities, and
  •          further explore toxicity mechanisms and the potential for their mitigation via therapeutic interventions.

The project hopes to lay the foundations for new Europe-wide standards in drug development. The interdisciplinary imSAVAR consortium is made up of 28 international partners from 11 nations and is being coordinated by the Fraunhofer Institute for Cell Therapy and Immunology (Leipzig, Germany) and Novartis. Partners include university and non-university research facilities, pharmaceutical and biotechnology companies, as well as regulatory authorities.

Organ-on-chip

The LUMC will participate in the development of novel immunocompetent in-vitro tissue models with focus on microphysiological systems (MPS), especially organ-on-chip platforms. The LUMC will bring in expertise on (i) differentiation of pluripotent stem cells to cardiomyocytes, vascular cells and monocytes/macrophages; (ii) generation and characterization of patient-derived induced pluripotent stem cells;  (iii) genetic engineering of hPSCs; (iv) development of human (cardio) vascular disease models with an inflammatory cell component.  These technologies will be implemented in imSAVAR with view to including functional inflammatory cells with different tissue identities derived from (patient) hiPSCs.  

This project receives 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.

Further information on the project will be available from February 2020 on the website www.imsavar.eu.

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