Fraunhofer Institute for Cell Therapy and Immunology IZI
Contact Press / Media
Dr. Conny Blumert
Head of Next-Generation Diagnostics Unit
Fraunhofer Institute for Cell Therapy and Immunology
Perlickstraße 1
04103 Leipzig, Germany
Phone +49 341 35536-3301
Medical Bioinformatics
AI-CARs
Currently, every year, around 24,000 people in Germany are diagnosed with malignant melanoma, i.e. black skin cancer, an extremely aggressive tumour with high metastatic potential. In spite of modern treatment methods, the 10-year survival rate of patients in the metastasized stage is below 20 percent.
So far, considerable success has been achieved in treating malignant melanoma with antibodies (so-called immune checkpoint inhibitors) which inhibit the activity of tumour-masking proteins. This, in turn, reactivates the body’s immune response to the tumour. However, a majority of patients (60 percent) does not respond to these treatments and the recurrence rate is high.
The CAR-T cell treatment, which has already been established in haemato-oncological applications, now also provides new options for the treatment of solid tumours, such as malignant melanoma: For this treatment, the patients’ immune cells are equipped with a synthetic receptor which enables the immune cells to detect potential cancer cells and specifically eliminate them in future.
As part of the “AI-CARs” project, the partners first want to define new target structures for treating malignant melanoma using human tumour samples and to subsequently develop an effective CAR-T cell treatment during the pre-clinical phase.
To this end, Fraunhofer IZI will use state-of-the-art sequencing technologies (single cell sequencing and spatial sequencing) to define potential target structures first. This involves the collection of highly complex datasets reflecting the cells’ dynamic behaviour. In cooperation with Leipzig University, effective interacting molecule pairs and specific target structures will be identified from these data, e.g., using artificial intelligence methods and computer-assisted modelling.
The Helmholtz-Zentrum Dresden-Rossendorf will develop CAR-T cells specifically for these target structures on the basis of a RevCAR-T platform and then test these pre-clinically. Unlike conventional CAR-T cells, RevCAR-T cells cannot directly detect tumour cells. They need an additional tumour-specific target model. As a result, the activity of the RevCAR-T cells and, hence, side effects can be controlled via the target modules’ availability.
Partners
Leipzig University Hospital, Department of Dermatology, Venereology and Allergology; Leipzig University, Drug Development Department; Helmholtz Zentrum Dresden Rossendorf, Radio-Immunology Department
Duration
06/2024 – 05/2027
SaxoCell
SaxoCell is a consortium of regional research institutions, clinics, and companies that jointly aim to establish an internationally competitive research and business cluster in Saxony focused on cell and gene therapies. The goal is to develop novel gene and cell therapeutics, known as “living drugs.” SaxoCell is funded by the Federal Ministry for Research, Technology, and Space through the innovation competition "Clusters4Future."
Duration
08/2024 – 07/2027
sc-RNA sequencing and spatial transcriptomics in multiple myeloma in collaboration with Leipzig University Medical Center and other partners
Functional control of therapeutic CARs (e.g., CAR-T cells, CAR-NK cells) and monitoring of therapy success in patient samples at various time points based on clinical samples.
Duration
2023–2026
imSAVAR
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
CERTAINTY
The goal of CERTAINTY is to transform the way cancer is treated through a personalized approach. As part of this project, a virtual twin will be created to analyze and predict the interaction of the individual CAR T cell product with the individual patient.
More information: www.certainty-virtualtwin.eu
SniffBot
Development of a fully automated health kiosk for analyzing respiratory diseases using respiratory diagnostics
During the coronavirus pandemic, there has been a growing desire to identify infected individuals quickly in order to reduce further transmission. This requires fast and cost-effective tests that can be used for mass screening, e.g., at the entrances to hospitals, nursing homes, or pharmacies. SniffBot's goal is to develop a technical and fully automated solution for this purpose. We rely on the analysis of volatile organic compounds (VOCs) in exhaled air. These are analyzed within 2–4 minutes using ion mobility spectrometry (IMS). This IMS method makes it possible to distinguish between bacterial and viral pathogens or to determine the exact virus type. The project focuses on the development of an automated communication and sampling tool on the one hand and automated data evaluation on the other. Upon completion of the project, a fully automated health kiosk will be available where all steps are performed autonomously and automatically, i.e., no operating personnel are required.
Partners
United Robitics Group GmbH; Dr. med. Thomas Lipp, Praxis Dres. Lipp & Amm; + another industry partner
Duration
05/2024 – 04/2026
BreathAlert
Detection of antibiotic-resistant bacteria using ion mobility spectrometry
In a report, the World Health Organization emphatically describes why the fight against antibiotic resistance is one of the major tasks faced by the global community. By the year 2050, the organization expects 10 million deaths annually that will be attributable to infectious agents [1]. Innovations are necessary not only for therapeutic treatment, but also for the diagnostic detection of pathogens that cause disease to counteract the challenge in the healthcare sector.
The BreathAlert project launched at the end of 2020 aims at improving this situation with a new method for the rapid and non-invasive detection of infectious agents and antibiotic resistance, which analytically analyzes patients’ breath. The project focuses on the further development of ion mobility spectrometry, which is to be used to characterize volatile organic components (VOCs) of microorganisms.
At the Fraunhofer IZI, selected microorganisms are being examined to determine whether they can be differentiated via the VOCs released and whether they can be assigned to the respective types of bacteria. For this purpose, the pathogens are first cultivated and then the headspace, the gas phase above the culture medium, is fed into the device. The VOCs are ionized, separated in an electric field and then detected at different times. Software analyzes the complex data. The aim is to identify specific signals with which bacteria can be reliably differentiated from one another, even under different conditions. The focus is on antibiotic-resistant pathogens, such as enterobacteria, which are increasingly showing resistance to carbapenem and cephalosporin [1].
The characterization of clinical isolates, air samples from infected patients and measurements of the influence of e.g. eating habits on the air we breathe round off the project.
The company Graupner medical solutions GmbH, which develops the medical device technology, works together with the Fraunhofer IZI as a consortium partner. The development work is supported by specialist clinics that provide access to samples and also carry out a final validation. The project results are used economically by the Graupner company.
1] World Health Organization Report 2017: Prioritization of Pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. WHO/EMP/IAU/2017.12
Duration
12/2020 – 11/2023
M3Infekt
Probandentest zur Atemluftanalyse.
Non-invasive diagnostics by breath analysis
Exhaled air contains substances known as volatile organic compounds (VOCs), which provide information about metabolism. In a variety of diseases, including infections, cancer and neurodegenerative diseases, the metabolism and thus the composition of the exhaled VOCs changes. Detection of these VOCs offers the opportunity to diagnose diseases early and non-invasively.
Ion mobility spectrometry (IMS) can detect VOCs within minutes directly at the point-of-care. The BMBF project ”Breath Alert” investigates whether IMS can be used to detect antibiotic resistance in bacteria. In the Fraunhofer-versus-Corona cluster project ”M3Infekt”, IMS technology was further developed at the Fraunhofer Center Erfurt FZE with the participation of Fraunhofer IZI. Specifically, methods for sampling via mouth and nose, for short-term sample preservation and for sample preparation were established and tested. At the end of the project, the method was tested on 60 healthy volunteers in two clinical studies in Dresden and Magdeburg. In parallel, a functional novel IMS demonstrator was completed at Fraunhofer FZE. This must now be further developed and optimized in follow-up projects to selectively detect diagnostics-relevant VOCs in complex matrices such as exhaled breath.
In the M3Infekt project, the participating nine Fraunhofer Institutes developed further non-invasive and mobile sensors for recording heart rate, ECG, oxygen saturation, respiratory rate and respiratory volume. Concepts for system integration and flexible interfaces were defined and a multimodal AI framework for cross-sensor data evaluation was developed. In addition, requirements regarding conformity to medical regulatory requirements were developed. The overall vision of the project is a close monitoring of relevant clinical parameters for detecting condition deterioration in infectious diseases also outside of intensive care units via a multimodal, modular and mobile sensor system. During the project it has become apparent that several specific solutions for different sub-applications are more useful than a single overall system and thus the benefit of the project results is even increased.
Duration
09/2020 – 09/2021
MOCHA
Mobile Organ-on-Chip Analytics
Organ-on-chip technology enables the exploration of complex cellular processes in lab-on-chip systems with minimal cell material. It accelerates drug development, enhances safety and cost efficiency, and reduces the risk of failure due to species differences by utilizing human models. The combination of microfluidics, 3D cell culture, spheroids, and organoids creates in vivo-like conditions. However, this currently requires elaborate infrastructure (e.g., hypoxic environments), which complicates access to high-resolution, multiparametric analytics (microscopy, spectroscopy).
MOCHA aims to develop a compact, chip-based analysis unit that integrates optical and non-optical methods to enable comprehensive monitoring. Through intelligent fluidic design and appropriate material combinations, long-term cultivation of spheroids over weeks to months is intended. A microfluidic platform will be developed to ensure in vivo-like supply, controlled nutrient and gas delivery, efficient metabolite removal, interactions between spheroids, and targeted drug delivery. Spheroid layouts, fluidic routing and actuation modules, and sensor integration interfaces will be developed. Additionally, an operating device for thermal and fluid control with integrated sensors and real-time data retrieval via suitable interfaces will be created.
Duration
07/2024 – 06/2027
MIC-PreCell
MIC-PreCell established a technology hub at the Fraunhofer Center Erfurt FZE for precise quality assurance and process control in the production of cell-based therapeutics (ATMPs). Under the leadership of the Fraunhofer Institutes IZI (Cell Therapies), IPMS (Microelectronics / MEMS), and IOF (Optics / Photonics), novel, automatable analytical methods are being developed and made transferable to GMP-compliant workflows. The goal is to reduce manufacturing costs, detect process risks at an early stage, and enhance product consistency for patient-specific and off-the-shelf therapies (e.g., CAR-T, CAR-NK, stem cells). This approach addresses key bottlenecks in current quality control: Many tests are currently performed sequentially, invasively, and are not inline-capable, meaning that errors often only become apparent at the end of costly processes. MIC-PreCell closes this gap with three complementary technology modules:
- Mechanomics: Real-time deformability cytometry (RT-DC) captures label-free biomechanical cell parameters as sensitive functional markers (activation, stress, differentiation) and enables stop / go decisions during expansion and transduction.
- Volatilomics: GC-IMS-based gas analytics quickly, robustly, and non-invasively detects volatile metabolites (VOCs) from cell cultures – for density / growth monitoring, stress and contamination detection, as well as the optimization of cultivation conditions.
- Micro-manipulation: A modular probe station with high-resolution imaging and MEMS micro-grippers / micro-injectors allows for precise interventions and functional tests on single cells, spheroids, and organoids.
Additionally, the cell culture infrastructure at Fraunhofer FZE is being expanded for complex human cells (T / NK cells, stem cells, tumor material), and standardized SOPs are being implemented. Data analysis pipelines using machine learning link mechanical, metabolic, and imaging signatures to practical QC parameters.
Duration
09/2021 – 06/2023
AutoImmunCAR
AutoImmunCAR investigated the transferability of the successful CAR T-cell therapy from oncology to B cell-mediated autoimmune diseases. Building on the MIC-PreCell infrastructure available at the Fraunhofer Center Erfurt (FZE) and in close collaboration with the Central German Cancer Center (CCC Jena Leipzig), proof of concept results were achieved for new analytical methods that characterize interactions between T- and B-cells in high resolution. The goal was to create an integrated picture of immunological, biomechanical, and metabolic parameters to capture activation, function, and potential efficacy markers of native and CAR-transduced immune cells.
Key methods included:
- Flow Cytometry with a customized panel (based on the clinical panel of the University Hospital Leipzig) for phenotyping and activation analysis.
- Real-time Deformability Cytometry (RT-DC) for label-free capture of biomechanical cell signatures.
- Gas Chromatography-Ion Mobility Spectrometry (GC-IMS) for non-invasive metabolic profiling (VOC analytics).
In a seven-month project timeframe, simple yet meaningful cell models were established: baseline T-cells and hyperactive B-cells as an autoimmune phenotype, supplemented by mixed T / B cell cultures. Based on this, reference profiles of resting and activated cell populations (native and CAR-modified) were created, along with initial datasets on changes following direct cell-cell interactions. The combination of surface marker expression (flow cytometry), mechanical properties (RT-DC), and metabolic signatures (GC-IMS) demonstrated the potential to complementarily and early capture activation states, stress responses, and functional differences.
Duration
05/2024 – 11/2024
LIFE-Koop 2024
The aim of LIFE KOOP 2024 is to investigate the relationship between microclots in the blood and the brain health of participants in the LIFE Adult studies. To this end, the quantity, concentration, and characteristics of microclots in existing LIFE Adult samples from the Leipzig Medical Biobank (LMB) will be analyzed and linked with data from the LIFE database. Microclots are insoluble, very small blood clots overloaded with inflammatory molecules that can be detected in the blood capillaries of patients with severe courses of COVID-19 and Long-COVID. They can severely disrupt the supply of oxygen and nutrients, potentially triggering COVID-associated neurological and psychiatric symptoms such as muscle pain, fatigue, or brain fog. Microclots are also detectable in patients with Type 2 diabetes, Alzheimer’s, or Parkinson’s disease.
The focus of the current project is to investigate a possible correlation between the concentration of microclots in the blood, cognitive parameters, and the structure and function of the brain, further specified through the inclusion of MRI parameters from the LIFE cohorts. It is expected that microclots will be associated with aging processes in the brain and mediate vascular-related neurodegenerative structural and functional changes. The planned investigations will contribute to predicting and better understanding cognitive decline and an increased risk of dementia.
Duration
05/2024 – 12/2027
Smart µ-Plate
The goal of Smart-µ-Plate is to develop a fast, cost-effective analysis system for bedside detection of specific biomarkers in human samples. Miniaturized sensor components will be integrated with customized bioassays and user-friendly hardware into a portable solution.
Duration
01/2024 – 12/2026
Glyco3Display
Glyco3Display focused on the integration of synthetically produced sugar / glycan molecules into DNA-based nanoparticles to create hybrid nanostructures that target bacteria and viruses for both diagnostic and therapeutic purposes. Sugar molecules such as mannose or sialic acid are common molecules for recognition and binding between biological organisms, including cells, viruses, and bacteria. In Glyco3Display, DNA-based nanoscaffolds were used to generate nanometer-precise arrangements of sugar molecules, which were then utilized to bind bacteria such as E. coli and integrated into various systems for the detection and analysis of binding to different bacteria, viruses, and sugar-binding proteins known as lectins.
Duration
01/2018 – 06/2023
MOTION
The project focuses on the development of technologies for cell- and tissue-specific nanocarriers. Various targeting components are integrated into nanocarriers made of lipids or amphiphilic polymers to enable the targeted delivery of cargos to target cells.
Duration
07/2022 – 12/2025
CoronaSense
In CoronaSense, nanostructures made from a combination of DNA strands and peptides were used to investigate the binding of the SARS-CoV-2 spike protein to target protein sequences. A peptide fragment mimicking the binding site of the spike protein on the ACE2 antigen was chemically conjugated to a DNA nanostructure in a multivalent arrangement that resembles the natural geometry of the spike protein. This DNA-templated binding was utilized to study the cooperativity between the subunits of the spike protein during binding and to assess the effects of natural mutation variants that occur during SARS-CoV-2 infections.
Duration
06/2020 – 05/2021
AsphyxDX
The goal of the AsphyxDX project is to translate extensive existing preliminary work in the detection of oxygen deprivation (asphyxia) in newborns into diagnostic applications. The diagnostic approach is based on the quantification of small endogenous metabolites (molecular weight <1200 Da); this will be performed for diagnostics (independently of large devices such as mass spectrometers) using nanopore-based and other rapid tests. Novel point-of-care (PoC)-capable testing systems are to be developed for this purpose. The role of Fraunhofer IZI is to develop functionalized DNA-based nanostructures that bind to the selected metabolites through specific ligand-receptor interactions.
Funding
Forum Gesundheitsstandort Baden-Württemberg
Duration
06/2020 – 05/2022