Press release from Heidelberg University Hospital (UKHD)

In the PRECISION ImmunoRad project, scientists from Heidelberg, the US, and Cyprus are pooling their expertise to optimally combine modern therapeutic approaches against tumors that have been difficult to treat to date and to exploit the synergistic potential of immunotherapy and precision-guided radiation therapy. High-precision ion beams, modified immune cells (CAR-T), personalized cancer vaccines, and the targeted reprogramming of the tumor microenvironment are being used. The European Research Council (ERC) is awarding the ERC Synergy Grant for this pioneering research project with a total funding amount of €14 million over the next six years. The international project is being coordinated by the Heidelberg Medical Faculty of Heidelberg University. €5.5 million of the funding will go to projects in Heidelberg.

An international research project conducted by Heidelberg University's Medical Faculty in collaboration with the German Cancer Research Center (DKFZ), the University of Pennsylvania (USA), and the Cyprus Cancer Research Institute (CCRI) has been awarded the prestigious ERC Synergy Grant from the European Research Council (ERC) for the joint project “PRECISION ImmunoRad.” The aim of the project is to transfer the successes of immune cell-based therapies in the field of blood cancers to solid tumors. In preliminary work, the teams have already identified the key factors that cause solid tumors to be resistant to immunotherapies and not respond to CAR-T cell therapies. Now, the researchers want to specifically reprogram the interaction of the tumor with immune cells in the immediate tissue environment (immunological microenvironment) so that they can effectively fight the tumor. To this end, the scientists are combining high-precision ion beams and CAR-T cell therapy—two of the most precise approaches in modern cancer medicine. In addition, methods of “molecular engineering” are used to specifically modify the immunological tumor microenvironment, as well as personalized cancer vaccines.

The ERC Synergy Grant is considered one of the most competitive awards in European science. With it, the ERC supports outstanding researchers in realizing groundbreaking ideas that can only be implemented by specialized teams working together. The funding volume is €14 million over six years.

The coordinator of the international collaboration is Prof. Dr. Dr. Amir Abdollahi, Heidelberg University Medical Faculty and Heidelberg University Hospital (UKHD), Executive Director at the National Center for Tumor Diseases (NCT) Heidelberg. “With this unique combination of ion beam, cell, and immunotherapy, we want to lay the foundation for a new generation of precise, personalized cancer therapies in which the immune system itself becomes the strongest ally against previously therapy-resistant tumors,” says Prof. Abdollahi. “The close collaboration between leading research centers exemplifies how international cutting-edge research can jointly open up new avenues for more effectively combating difficult-to-treat cancers in the future.”

The subprojects are led by:

•  Prof. Dr. Amir Abdollahi, W3 Professor of Translational Radiation Oncology at Heidelberg University's Medical Faculty and Head of the Clinical Cooperation Unit of the same name at the German Consortium for Translational Cancer Research (DKTK) at the DKFZ, is a recognized expert in the fields of ion therapy and targeted reprogramming of the immunological tumor microenvironment.
• Prof. Dr. Dirk Jäger, Medical Director of the Department of Medical Oncology at Heidelberg University Hospital and Head of the Clinical Cooperation Unit “Applied Tumor Immunity” at the DKFZ, specializes in personalized immunotherapies.
• Prof. Dr. Constantinos Koumenis, currently Endowed Professor of Radiation Oncology at the University of Pennsylvania (UPenn), Philadelphia, USA, will establish a research group at the Cyprus Cancer Research Institute (CCRI) in Nicosia, Cyprus, as part of the project. He is an expert in FLASH proton therapy and the stress responses triggered by radiation in tumors and their microenvironment (integrated stress response).
• Prof. Dr. Carl H. June, Director of the Center for Cellular Immunotherapies at UPenn, is considered a pioneer in immune cell engineering and the father of CAR-T cell therapy.

“As a medical faculty, we are delighted about this fantastic award for the research team from the European Research Council,” says Prof. Dr. Michael Boutros, Dean of the Faculty of Medicine. “The transatlantic collaboration, which will be funded by the ERC Synergy Grant for the next six years, is particularly noteworthy.”

Ion irradiation and “molecular engineering” to support immune cells in fighting tumors

Particularly aggressive tumors such as pancreatic cancer have so far responded poorly or not at all to conventional forms of treatment. Not only are they resistant to radiation and chemotherapy, but they also evade the immune system by forming protective scar tissue (remodeling), releasing immunosuppressive substances into the immediate environment, or specifically reprogramming immune cells so that they no longer attack or tolerate the tumor. This prevents modern immunotherapies from being fully effective.

The aim of “PRECISION ImmunoRad” is to overcome the tumor's diverse immune shielding mechanisms. Previous work by the consortium has shown that this could be achieved through the combined use of ion beam therapy, CAR-T cell therapy, special agents for immune activation in the tumor environment, and personalized cancer vaccines.

Ion beam therapy—using protons, helium, carbon, or oxygen ions, for example—destroys tumor cells with extreme precision while sparing surrounding healthy tissue. At the same time, it breaks down tumor structures and stimulates immune responses, making the tumor visible to the immune system. By destroying immune-suppressing cells and signaling pathways in the tumor, the irradiation prepares the ground for CAR-T cell therapy. For this purpose, the body's own immune cells are removed and genetically modified outside the body so that, once back in the patient's body, they recognize and attack the tumor. Thanks to the preparatory effect of ion beam therapy, CAR T cells should in future also be able to reach tumors that were previously shielded from the immune system. "Both ion beam therapy and CAR T-cell therapy are, in a sense, the moon landings of cancer medicine. In order to defeat resistant tumors in the future, we will exploit the full synergistic potential of these therapies in our joint project,“ said Prof. June. ”This transatlantic alliance between Heidelberg University and the University of Pennsylvania brings together two world-leading research programs in a joint mission to fundamentally transform cancer treatment."

Combination with personalized cancer vaccines

This approach is complemented by personalized cancer vaccination. This involves identifying characteristic molecules – known as tumor antigens – from the respective tumor. Based on these, the scientists produce an individual vaccine from synthetically produced tumor antigens, which specifically “trains” the body's own immune system to recognize the specific tumor characteristics. “We hope that with these vaccines, in combination with precision radiation and immune cell therapies, we may be able to build up an immune memory for a long-lasting tumor defense response. That would be a milestone in the development of highly individualized and effective cancer therapies,” says Prof. Jäger. Prof. Koumenis' team will identify new targets for both CAR T cells and personalized vaccines. “The goal is to make new findings available to the consortium's clinical trials as quickly as possible so that patients can benefit from this collaboration at an early stage,” says Prof. Koumenis. 

"I am deeply impressed by how the pioneering work in ion therapy in Heidelberg has gone far beyond the original goal of anatomical precision. Now it has the potential to enable new treatment options for broad application in cancer medicine, not only in terms of precise radiation, but also as a door opener for immune cell therapy," says Prof. Dr. Dr. Jürgen Debus, Medical Director of the Department of Radiation Oncology and Chairman of the Board of the UKHD. Under his leadership, the globally unique Heidelberg Ion Beam Therapy Center (HIT) was established in 2009.

Further information on the Internet

ERC press release

Contact

Dr. Carmen D. Klein Bonilla 
Coordination Office Radiation Oncology Program
Clinical Cooperation Unit Translational Radiation Oncology
German Cancer Research Center (DKFZ) and Heidelberg University Hospital (UKHD)
National Center for Tumor Diseases (NCT) Heidelberg
Tel.: 06221 56-310695
Email: carmen.klein(at)nct-heidelberg.de

This press release is also available online in our UKHD Newsroom
 

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Heidelberg University Hospital (UKHD) is one of the most important medical centers in Germany, and Heidelberg University's Medical Faculty is one of Europe's internationally renowned biomedical research institutions. Their common goal is to develop innovative diagnostics and therapies and to implement them quickly for patients. The hospital and faculty employ around 14,500 people and are committed to training and qualification. In more than 50 clinical departments with around 2,500 beds, approximately 86,000 patients are treated annually on an inpatient and day-care basis, and more than 1,100,000 patients are treated on an outpatient basis. Together with the German Cancer Research Center (DKFZ) and German Cancer Aid (DKH), the UKHD has established the first National Center for Tumor Diseases (NCT) in Heidelberg. The aim is to provide the highest level of care as a leading oncology center and to quickly transfer promising approaches from cancer research to the clinic. In addition, the UKHD, together with the DKFZ and the University of Heidelberg, operates the Hopp Children's Tumor Center Heidelberg (KiTZ), a therapy and research center for oncological and hematological diseases in children and adolescents that is unique in Germany.The Heidelberg Curriculum Medicinale (HeiCuMed) is at the forefront of medical education in Germany. Currently, around 4,000 prospective doctors are studying and pursuing doctorates at the Heidelberg Medical Faculty (MFHD). www.klinikum.uni-heidelberg.de

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