Fraunhofer Institute for Cell Therapy and Immunology IZIBioinformatics
In recent years, immunotherapies, such as CAR-T cell therapies, have shown great success in hematologic malignancies. However, major challenges remain. Here, we use in-silico methods to elucidate molecular mechanisms that influence the mode of action and the occurrence of side effects as well as treatment resistance of immunotherapies. We are developing biomarkers that can be used for robust quality control of the manufacturing process as well as for the identification of patient groups that benefit from immunotherapy.
Development of innovative model systems for the evaluation of immunomodulating therapeutics
A significant challenge facing the development of immunomodulating therapies is their preclinical evaluation in terms of efficacy and safety. The greatest problem here is the complexity of the human immune system. The EU consortium imSAVAR (Immune Safety Avatar: nonclinical mimicking of the immune system effects of immunomodulatory therapies) is addressing these challenges by coming up with new ways of examining immunomodulatory therapies. Existing model systems are to be improved and new ones developed in order to identify adverse side effects of new therapies affecting the immune system. Furthermore, new biomarkers for diagnosing and predicting immune-mediated pharmacology and toxicities will be developed. The focus is also on more detailed research into toxicity mechanisms and the potential for their mitigation via therapeutic interventions.
The interdisciplinary imSAVAR consortium is made up of 28 international partners from 11 nations and is being coordinated by the Fraunhofer IZI and Novartis. Partners include university and non-university research facilities, pharmaceutical and biotechnology companies, as well as regulatory authorities.
Besides coordinating the overall project, Fraunhofer IZI focuses in particular on predicting and evaluating adverse effects caused by novel immunotherapies specifically developed for oncological and inflammatory diseases. This involves optimizing and developing respective models (in situ, in vitro, in vivo, in silico) and biomarkers that take into account the highly complex modes of action typical of immunotherapies.
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.
T2Evolve – accelerating development and increasing awareness and access of patients with cancer to immunotherapy
T2EVOLVE is a new breakthrough alliance of academic and industry leaders in cancer immunotherapy under the European Union’s Innovative Medicines Initiative (IMI). The key objective of T2EVOLVE is to accelerate development and increase awareness and access of cancer patients to immunotherapy with immune cells that harbor a genetically engineered T-cell receptor (TCR) or synthetic chimeric antigen receptor (CAR). Simultaneously, T2EVOLVE aims to provide guidance on sustainable integration of these treatment into the EU healthcare system.
Within the project we will use single-cell and spatial transcriptomics for toxicity and efficacy assessment of engineered T-cell or CAR T-cell therapies.
Project coordination
University Hospital Würzburg
Grant Agreement No
945393
Targeted Design of Natural Killer Cells for Immunotherapy of Acute Myeloid Leukemia
The overarching goal of this consortium project funded by the German Cancer Aid is the development of an effective CAR-NK immunotherapy for AML patients. We investigate the influence of factors in the microenvironment on the activity on CAR-NK cells using NGS analyses from patient material and model systems. Additionally, we accompany the GMP-conform production process for CAR-NK cells with NGS analyses and corresponding bioinformatics to identify intrinsic factors of NK cells for a successful production process.