PD Dr. Jennifer Altomonte
Klinikum rechts der Isar, Technical University of Munich
Commercialization of oncolytic viruses (FUSIX Biotech)
Oncolytic viruses (OVs) now claim a steadily growing market share in cancer therapeutics. These viruses offer an elegant and multimodal mode of action that enables a long-lasting systemic therapeutic success. Despite great progress, oncolytic viruses still face some obstacles in aggressive solid tumors and in reaching the tumor during intravenous application. FUSIX Biotech addresses these and other problems with a novel proprietary hybrid virus technology. Based on cell-cell fusion reactions, both the infection of healthy cells and the release of new virus particles from infected cells into the surrounding tissue are reduced, resulting in a special safety profile. With this funding, the team hopes to enable the preclinical development of its lead product.
Prof. Dr. Sebastian Kobold
Prof. Dr. Stefan Endres
Hospital of the Ludwig-Maximilians-Universität München
Development of a T-cell therapy platform to protect chimeric antigen receptor (CAR) T-cells and other cell therapeutic procedures from suppression and to apply regulatory mechanisms for function amplification (CARMOUFLAGE)
The use of chimeric antigen receptor (CAR) T cells has been established in the treatment of some leukemias and lymphomas. In contrast, CAR-T cells are not effective in solid tumors due to tumor-associated immunosuppression and insufficient access of T cells to tumor cells. The research team led by Dr. Sebastian Kobold therefore developed the CARMOUFLAGE platform to enable the access of CAR-T cells to tumor tissue. At the same time, a receptor protecting against immunosuppression increases the cytotoxic activity of CAR-T cells. The funding is intended to confirm the effect of CARMOUFLAGE and to demonstrate the therapeutic safety of the approach.
Dr. Hannelore Meyer
Dr. Grzegorz Popowicz
Dr. Krzysztof Zak
Technical University of Munich
Development of novel antibiotics for the treatment of infections with multi-resistant Gram-negative bacteria (FRAgment based antiBIOTICS - FRABIOTICS)
Infections with multi-resistant bacterial pathogens represent one of the greatest medical challenges of the future. Using its own screening platform, the research team was able to identify two novel fragment classes as inhibitors of bacterial resistance against the most important antibiotic class, the β-lactame-antibiotics. The combination of active inhibition of all β-lactamase classes with an independent antibacterial effect opens up the possibility of developing a drug with a double mode-of-action and thus making new resistance development considerably more difficult. Within the m4 Award, the inhibitors are to be further optimized with regard to their antibacterial effect.
Dr. Benjamin Kick
Dr. Klaus Wagenbauer
Dr. Jonas Funke
Technical University of Munich
Development of a nanoswitch for antibodies (LOGIBODY)
Antibody-based immunotherapies have great potential for the treatment of tumor diseases. However, an over-stimulation of the immune system can lead to side effects that require the therapy to be discontinued. This overstimulation has two causes: First, the target antigens are often present both on the tumor tissue and on the healthy tissue. Secondly, the antibodies are active throughout the body and not only locally on the tumor. In order to solve these problems, the team and its mentor Prof. Dietz have developed an "on/off button" for antibody immunotherapies. This is an ultra-miniaturised nanoswitch made of DNA. The nanoswitch can specifically recognize tumor cells and recruit the body's own immune cells to fight these cells. This enables the immune system to fight tumor cells in a targeted and "on demand" manner and leads to lower activity on healthy tissue and thus to fewer side effects. In the medium term, the LOGIBODY platform will be used in cooperation with pharmaceutical companies to develop therapeutics against various tumor diseases. If the technology is successfully validated, LOGIBODY's own therapies are planned in the long term. LOGIBODY is an example of the innovative potential of molecular robotics.
Prof. Dr. Stephan Sieber
Dr. Franziska Mandl
Dr. Mathias W. Hackl
Dr. Christian Fetzer
Technical University of Munich
Preclinical development of a resistance-free antibiotic for the treatment of fatal infectious diseases (aBACTER)
Bacterial infectious diseases caused by multi-resistant organisms such as multi-resistant Staphylococcus aureus (MRSA) pose one of the greatest dangers to our health. The project team around Prof. Dr. Stephan Sieber has discovered a new antibiotic, which is very effective against gram-positive, multi-resistant bacterial strains and shows no development of resistance. The new mode of action differs fundamentally from that of all previously approved antibiotics. The primary goal of the aBACTER project is the development of a new antibiotic against endocarditis, an inflammation of the inner lining of the heart that is already very difficult to treat.
Prof. Dr. Anja Bosserhoff
Prof. Dr. Claus Hellerbrand
The melanoma (black skin cancer) is the most frequently fatal skin disease with a worldwide increasing number of incidences. The protein MIA promotes dangerous melanoma metastasis and prevents the immune system from fighting the tumor. Prof. Bosserhoff and Prof. Hellerbrand were able to reveal the mechanism of the MIA effect on the melanoma cells and to develop substances with which MIA can be inhibited. Such peptide-based, intravenously administered substances already had a significant effect in the mouse model. Now the researchers aim to develop orally available small molecules, for example in the form of a tablet. Thus they want to provide melanoma patients with a highly specific, effective and compatible therapy at the same time.
Prof. Dr. Matthias Mack
Dr. Kerstin Renner
About 2.5 million people worldwide live with multiple sclerosis. Up to 90% of the patients suffer from a type of the autoimmune disease with acute exacerbations. For the treatment of the inflammatory reactions due to an attack, mainly highly dosed steroids such as cortisone are available, to which about 40 percent of the patients are not adequately responsive and therefore cause accumulating damage. Therefore Prof. Mack and Dr. Renners follow the approach of a combination of steroids and a humanized antibody. The antibody is directed against so-called monocytes, which carry the surface protein CCR2. These immune cells, which are responsible for tissue destruction, are to be removed by antibody therapy for a short period in order to keep the cerebral tissue damage at MS exacerbations low. With the funding, the team will investigate the synergistic effects of steroids and CCR2 antibodies in preclinical studies.
Dr. Valentin Bruttel
Prof. Dr. Jörg Wischhusen
About 5-10% of the population of Western industries suffer from autoimmune diseases. Here, the immune system is directed against the body by an overreaction. However, current therapies suppress not only these harmful immunoreactions, but also protective ones against e.g. pathogens or tumor cells. This leads to severe side effects, which are not observed during pregnancy, although also here immune reactions have to be suppressed against the tissue of the embryo which is partly derived from the father. In the working group of Prof. Wischhusen at the University Hospital in Würzburg, Dr. Bruttel has discovered a novel mechanism, which, in pilot experiments, allows exactly such a targeted and effective suppression of individual immune reactions. Based on this, the platform technology AIM Biologicals was developed, which is now to be adapted and thoroughly tested within the context of the m4 Award promotion for neuroinflammatory autoimmune diseases such as multiple sclerosis (MS) or neuromyelitis Optica (NMO). Bruttel and his colleagues have set themselves the goal of developing drugs which can be administered easily but nevertheless stop harmful autoimmune reactions very targeted and with low side effects.
Dr. Marcus Conrad
Dr. Bettina Proneth
Helmholtz Zentrum München
For the development and maintenance of multicellular organisms, it is essential to kill individual cells in a targeted manner. This is the only way to achieve a balance between cell growth and cell death. One form of regulated cell death is ferroptosis. Conrad and colleagues utilize this mechanism to destroy targeted tumor cells. The researchers have shown that the fatty acid metabolism enzyme ACSL4 plays a central role in ferroptosis. Cells carrying this enzyme are sensitive to cell death regulation. There is no targeted treatment of a particular form of breast carcinoma, the most common cancer in women - these patients have the worst survival outcomes. However, the enzyme ACSL4 is found in the tumor cells of this breast cancer form. The project aims to find ferroptosis triggering substances by means of a newly established screening platform and to further develop these for testing in relevant tumor models.
Dr. Jonas Helma-Smets
Dr. Dominik Schumacher
Prof. Dr. Heinrich Leonhardt
Prof. Dr. Christian Hackenberger
The classical cancer treatment with chemotherapy and/or irradiation brings many side effects, as the means generally nonspecifically affect the whole body. Targeted tumor therapy, on the other hand, tries to kill only cancer cells. Widely considered a major new hope are antibody-drug conjugates (ADC), which consist of three components: the antibody targeting a specific protein which is preferably only present on the tumor cell, a cell toxin that is to attack the tumor as well as the so-called "linker", which connects the other two components. This linker is particularly important because it ensures that the active substance is released only after binding to the tumor cell. By its proprietary technologies the research team at the LMU Munich and the FMP Berlin is developing a kind of molecular glue for the stable attachment of the toxins and thus the production of effective and compatible ADC at the same time. Within the scope of the m4 Award, a first own ADC for the treatment of acute myeloid leukemia (AML) is to be tested preclinically.