idw – Informationsdienst Wissenschaft
Nachrichten, Termine, Experten
Nachrichten, Termine, Experten
ERC Starting Grant for Karl Petri: Würzburg researcher develops new technology for a safe and long-lasting in vivo CAR-T cell therapy
Würzburg. To date, CAR-T cells have been produced outside the body. For this purpose, T cells are obtained from the patient's blood and genetically modified in the laboratory so that they produce proteins on their surface known as chimeric antigen receptors (CARs). These CARs help T cells recognize and destroy cancer cells. After being reprogrammed, the CAR-T cells are transferred back into the body. Since their first approval in 2017, CAR-T cells have fundamentally changed the treatment of selected blood cancers, including certain forms of leukemia, lymphomas, and multiple myeloma. In some patients, they can achieve long-lasting remissions.
ERC Starting Grant worth 1.5 million euros
However, personalized production in the laboratory is associated with considerable time and cost and is not always successful. Dr. Karl Petri from the Chair of Cellular Immunotherapy and the Department of Medicine II at University Hospital Würzburg (UKW) aims to bypass this process in a new research project in the future. The CAR-T cells are to be generated directly inside the body. For this project, he is receiving an ERC Starting Grant from the European Research Council (ERC). The prestigious research award is endowed with almost 1.5 million euros.
CAR-T cells to be generated directly inside the body
“I was absolutely thrilled that our project was selected. It means that we can address an important and forward-looking research question,” says Karl Petri. “Immune cell therapies have enormous potential, not only in cancer medicine. What is still lacking is a truly efficient and safe technology for producing such therapies directly inside the body. We aim to close this gap by combining different technologies.”
For T cells to produce CARs inside the body, a vector is required. The vector can be of viral origin or take the form of nanoparticles. Conventional CAR-T cell production in the laboratory generally uses viral vectors. They introduce DNA containing the CAR gene into the T cells that have previously been removed from the body. The DNA is permanently integrated into the T cells' genetic material, allowing them to produce CAR proteins over the long term. However, it is not possible to fully control where in the genome viral vectors integrate. In in vivo CAR-T cell therapy, the risk may potentially be increased: the viral vectors are administered throughout the body and could therefore reach and genetically modify not only T cells but, under certain circumstances, other body cells as well.
An alternative delivery method is lipid nanoparticles. These tiny lipid particles can be used to safely introduce mRNA, the blueprint for CARs, into T cells. The disadvantage, however, is that this blueprint is very short-lived. This means that the T cells express the CAR protein on their surface for only a few days. The RNA molecule is then degraded, and the flow of genetic information required for CAR production ceases.
Combining the best of both approaches
“We now want to combine the best of both worlds: long-lasting CAR expression and a safe platform with targeted integration of the blueprint,” says Karl Petri. “To achieve this, we are developing a lipid nanoparticle-based in vivo CAR-T cell therapy using novel genome editing tools. This will place the genetic information of the CAR into a so-called safe-harbor region of the T cell genome, where it can safely remain.”
It is already known that lipid nanoparticles are generally suitable for transfecting T cells in vivo, i.e. for introducing genetic material into the cells in a targeted manner. Karl Petri has also already demonstrated that the new genome editing tools work in T cells. “Our preliminary data are very promising. The challenge now is to bring the components together and optimize the gene-editing tools so that the CAR blueprint reaches the T cells as efficiently, durably, and safely as possible.”
Safety checked at every step
Safety is an important part of the project. The team will carefully investigate every individual step and assess whether the treatment is safe and well tolerated. Among other things, the researchers will use analysis methods they have developed themselves. “For example, we investigate where the nanoparticles are distributed in the body and precisely determine where the genetic information is integrated into the cells' genome,” explains Petri.
Preparing for a clinical trial within five years
Over the next five years, he and his team aim to collect the necessary basic research and safety data from studies in cell cultures and mice. These data are intended to form the basis for a so-called Pre-IND meeting (Pre-IND stands for Pre-Investigational New Drug), which is intended to provide the basis for future clinical translation.
Strong partners at the Würzburg research location
The project is an example of the strengths and synergies of the Würzburg research environment. With Prof. Hermann Einsele, Director of the Department of Medicine II, and Prof. Michael Hudecek, Director of the Chair of Cellular Immunotherapy, two renowned CAR-T cell experts are based in Würzburg. Prof. Jörg Vogel, Managing Director of the Helmholtz Institute for RNA-based Infection Research (HIRI), is a recognized specialist in ribonucleic acids (RNA). In addition, structures such as the National Center for Tumor Diseases (NCT) WERA and the Bavarian Center for Cancer Research (BZKF) facilitate clinical translation. “If our plan succeeds, we will have a very strong platform for the in vivo generation and modification of cell therapies,” concludes Karl Petri.
The new project will also expand his research group: Petri plans to recruit two additional doctoral researchers and/or a postdoctoral researcher at the start of 2027. This would increase the current team, consisting of six scientists and one physician, to a total of nine members.
Part of the research group is already supported by funding from the German Research Foundation (DFG) through the Emmy Noether Programme. There, the team is developing novel CRISPR 2.0 tools to produce and further improve targeted CAR-T cell products for cancer treatment.
About Karl Petri
Dr. med. Karl Petri was born in Frankfurt am Main and grew up in Karben (Hessen). He studied medicine in Heidelberg and subsequently spent six years conducting research in the USA, at Massachusetts General Hospital and Harvard Medical School in Boston. Since summer 2023, he has been working at University Hospital Würzburg: at the Department of Medicine II, he leads an Emmy Noether research group at the Chair of Cellular Immunotherapy (Petri Lab). Karl Petri is married and has one son.
Dr. Karl Petri Petri_K@ukw.de
https://www.ukw.de/en/research-petri-lab/home/ Petri Lab
Karl Petri of the University Hospital of Würzburg has been awarded an ERC Starting Grant to work wit ...
Source: Daniel Peter
Copyright: UKW
Karl Petri's research group is looking for new members. Pictured here, from left to right, front row ...
Source: Christina Bornschein
Copyright: UKW
Criteria of this press release:
Journalists
Biology, Medicine
transregional, national
Contests / awards, Research projects
English
created with AI assistanceThe German press release was translated using AI and then edited by Karl Petri.
You can combine search terms with and, or and/or not, e.g. Philo not logy.
You can use brackets to separate combinations from each other, e.g. (Philo not logy) or (Psycho and logy).
Coherent groups of words will be located as complete phrases if you put them into quotation marks, e.g. “Federal Republic of Germany”.
You can also use the advanced search without entering search terms. It will then follow the criteria you have selected (e.g. country or subject area).
If you have not selected any criteria in a given category, the entire category will be searched (e.g. all subject areas or all countries).
