Prof. Hinrich Abken
Head of Research Division | Genetic Immunotherapy
In recent years, cellular immune therapies have shown high efficacy, demonstrating the power of the immune system in the control of cancer. Additionally, the immune system can be used to reduce autoimmune complications such as chronic inflammation or transplant rejection.
The aim of Professor Abken’s research is to explore these therapies and use tools to strengthen immune cells in the fight against cancer and autoimmune diseases. Our central strategy is based on T cells engineered with a chimeric antigen receptor (CAR)—a synthetic receptor. These immune cells are redirected towards specifically defined target cells, effectively acting as ‘living drugs’. The CAR recognizes and binds to a defined target structure on the tumor cell—activating the T cell to eliminate this target cell. To achieve this, T lymphocytes from the patient’s blood are engineered in the laboratory with a CAR, expanded, and reinfused to the patient in order to recognize and eliminate the tumor. Our scientists then equip these T cells with enhanced functionality, such as the ability to release an immune-modifying cytokine, which improves and prolongs CAR T-cell activation, and stimulates innate immune cells.
Below are key questions we seek to address in our CAR T-cell research:
- How do CAR T cells recognize tumor cells and which structures can be targeted?
- How can CAR T-cell fitness be enhanced?
- How can CAR T-cell selectivity and safety be improved?
- How can CAR T cells boost the overall immune defense against tumors?
- How can CAR T cells suppress autoimmune diseases?
- How can novel CAR T-cell research be progressed from concept to clinical exploration? (Translational research)
How do CAR T cells recognize tumor cells and which structures can be targeted?
The CAR binds to the cognate target structure on the cancer cell. This is predominantly achieved by using an antibody-derived binding domain. It is, as yet, unclear which target structures and which binding domains are the most complementary, and how the contact between CAR T cell and targeted cancer cell takes place. Our research seeks to gain a better understanding of this initial process so as to increase the efficacy of CAR T-cell therapies.
How can CAR T-cell fitness be enhanced?
On the one hand, tumors are able to actively suppress a CAR T cell’s immune response. On the other, T cells are also able to protect themselves against excessive activation and ultimately ‘exhaustion.’ Our goal is therefore to equip CAR T cells with enhanced functionality to resist suppression by cancer cells. Several strategies are currently being explored. These include: a synthetic receptor that counteracts negative signals; blocking checkpoints by inhibiting antibodies; and providing an additional cytokine signal to the T cell.
How can CAR T-cell selectivity be improved and the autoimmune response reduced?
Occasionally healthy tissue cells express some of the same target structures as cancer cells, although usually to a lesser degree. To prevent CAR T cells attacking healthy tissues, our research seeks to modify the CAR’s binding and/or signaling domain so that it selectively activates T cells in the tumor tissue. In close cooperation with Professor Simone Thomas, we are seeking to design a CAR that only activates T cells when they simultaneously bind to two antigens co-expressed on the same target cell.
How can CAR T cells boost the overall immune defense against tumors?
This branch of research focuses on engineering CAR T cells to release immune-activating substances, such as cytokines, into the tumor stroma. Such substances help to boost the body’s own immune response to the tumor and improve tumor control. This fourth-generation CAR—also known as TRUCKs (T-cells redirected for antigen-unrestricted cytokine-initiated killing)—specifically binds to its target tissue and activates the T cell to release immune-modulating cytokine or other mediators. As ‘living factories’ in the production of effective therapeutic substances, TRUCKs demonstrate significant potential for application in cell therapy which is yet to be fully exploited.
How can CAR T cells suppress autoimmune diseases?
The autoimmune reaction takes place when the immune system attacks the patient’s own tissues. In order to slow down this excessive immune response, we equip naturally occurring suppressor T cells (regulatory T cells) with a CAR to activate them when tissue is inflamed. This has the effect of repressing ongoing autoimmune reactions.
How can novel CAR T-cell research be progressed from concept to clinical exploration? (Translational reserach)
In close cooperation with Professor Simone Thomas, we are seeking to translate a novel CAR T-cell concept into an early-phase clinical trial. Specifically, this involves establishing the pre-clinical data sets for a CAR that blocks CD30-mediated T-cell repression while at the same time targeting cancer cells of gastrointestinal carcinoma.
Quote from Prof. Hinrich Abken
The immune system can successfully control cancer. Sometimes, however, this control becomes ineffective. In our research, we are developing tools that equip the immune cell to recognize, fight, and ultimately control cancer.
Head of Research Division Genetic Immunotherapy
Biography
Academic background and qualifications
Prof. Abken studied Medicine at the University of Essen. Graduating in 1983, he received Board certification in Biochemistry in 1996.
Professional career
Prof. Abken is Professor (W3) of Genetic Immunotherapy, University of Regensburg and has been Director of Genetic Immunotherapy Division, Leibniz Institute for Immunotherapy since 2018. Prior to this (1993–2018), he was Professor (C3) at the Clinic I of Internal Medicine, Medical Faculty, University of Cologne. From 1987–1993, he was Group leader, at the Institute of Genetics, Department of Molecular Genetics, Faculty of Sciences, University of Bonn. His career started in 1983 as a postdoctoral scientist at the Institute for Cell Biology, University of Essen.
Honors
In 2023 Prof. Abken was awarded the Johann Georg Zimmermann Medal.
Explore our Research Division in greater depth
Get to know our team and find out more about our pioneering research.