Featured Scientist
Profile
I am a physician-scientist working in the department of hematology and oncology at the University of Regensburg. For almost ten years, I have been involved in CAR T cell research seeking to improve the battle against refractory hematological malignancies and solid tumors with novel CAR T cells generated via synthetic biology. My particular interests are the identification of novel CAR target antigens, improving CAR T cells fitness, and the investigation of innovative CAR designs. To this end, I joined the group of Professor Hinrich Abken, pioneer in the field of CAR research, at the Leibnitz Institute for Immunotherapy in Regensburg. Furthermore, I teamed up with Professor Luca Gattinoni, who is a leading researcher in the field of T memory stem cells, to leverage the potential of CAR-modified T memory stem cells for the battle against cancer. Specifically, within the TRR 221 our project is centered on enhancing Graft versus leukemia responses using donor-derived CAR-modified CD8-positive T memory stem cells. Finally, we managed to acquire funding from German cancer aid to further refine the approach of CAR-modified T memory stem cells predicated on an early phase clinical trial enrolling patients with recalcitrant Richter-transformed large B cell lymphoma. After the completion of my residency, I intend to intensify my work on CAR T cells both regarding preclinical studies and with respect to conducting our early phase clinical trial.
interview to the authors
Who is the team behind project A07?
Project A07 is led by Prof. Luca Gattinoni at the Leibniz Institute for Immunotherapy and me at the University Hospital Regensburg. Prof. Gattinoni has been a pioneer in the study of T cell differentiation and memory subsets, and his work on stem memory T (TSCM) cells laid the foundation for this project. He was the first to identify this rare subset of T cells with stem-like properties and to establish a clinical-grade manufacturing platform for genetically modified TSCM cells, paving the way for a first-in-human clinical study.
I’m fortunate to work with a talented team, including Gabriele Inchingolo, a PhD student whose work has been central to understanding the molecular and functional features of engineered TSCM cells directly isolated from treated patients. What makes our project truly special is the close collaboration between experts in immunology, hematology, and cell engineering, an environment where clinical questions directly drive scientific discovery.
What do you consider the most important finding of this study? What are its main strengths and possible limitations?
This study conducted in collaboration with the US National Cancer Institute, represents a landmark in cellular cancer immunotherapy, as it is the first to report the clinical use of TSCM cells in the treatment of cancer. We demonstrated that in patients with relapsed lymphoma or leukemia following allogeneic stem cell transplantation, TSCM isolated from the original bone marrow donor and genetically engineered with a synthetic antigen receptor called chimeric antigen receptor (CAR) could safely and effectively target cancer cells.
The main strengths of the study lie in its innovative use of a highly potent and long-lived T cell subset, its clinical relevance in a high-risk and hard-to-treat patient population, and the favorable balance between efficacy and safety observed. Beyond the clinical relevance, our work highlights striking biological differences in the in vivo behavior of CAR TSCM cells compared to conventional CAR products, providing valuable mechanistic insights into how TSCM cells contribute to clinical efficacy and safety.
The major challenge ahead is to validate and expand these findings in larger patient cohorts, which remains one of our primary goals moving forward.
To what extent could these findings inform patient treatments or influence health policies?
The key finding of our study is that CAR TSCM cells are safe and associated with only mild toxicity compared to conventional T cell therapies. Importantly, they can induce complete remissions even at reduced cell doses. These results have significant clinical implications, as they support the initiation of follow-up clinical trials and the broader application of TSCM cells in treating patients with leukemia and lymphoma. As evidence continues to grow, these results could influence treatment guidelines and ultimately help position TSCM cells as a standard option in cellular cancer immunotherapy. In the long term, this may also shape health policy by supporting the integration of safer, more effective cell therapies into routine care.
What would you most like others to know about this study?
We want to emphasize that TSCM cells represent a powerful and versatile new approach in cancer immunotherapy. Compared to conventional T cell therapies, TSCM cells show improved effectiveness and reduced toxicity, especially in patients who experience relapse after allogeneic bone marrow transplantation. This makes them a promising option for patients with otherwise limited treatment choices.
How do you plan to build on this work in future research?
Our next step is to refine the CAR TSCM cell platform to achieve even more effective targeting of tumor cells. To this end, we have developed a new semi-automated manufacturing process for generating engineered TSCM cells and have designed a new clinical trial to be conducted in our medical center in Regensburg, which will focus on using CAR TSCM cells engineered with an improved bispecific antigen receptor to treat patients with aggressive lymphoma.
What inspired you to become a scientist? What do you love most about your work?
Early in medical school, I attended Cellular Therapy, a symposium organized by Andreas Mackensen in Erlangen, where leading scientists such as Professor Carl June presented recent advances in cellular cancer immunotherapy. This experience sparked a deep enthusiasm for the field and solidified my decision to pursue a career as a scientist. What I love most about being a physician-scientist is the close integration between treating patients and actively developing new therapies, thus bridging the gap between clinical care and cutting-edge research.
Dennis Harrer's Bio
Personal Data
Title: PD. Dr. med.
First name: Dennis
Surname: Harrer
Current position: Postdoc, resident
Current institution(s)/site(s), country:
University Hospital Regensburg
Department of Internal Medicine III – Hematology and Oncology
Germany
Identifiers/ORCID: Not applicable.
Qualifications and Career
Degree programme:
Medicine, 2012–2019, University of Erlangen, Germany
Doctorate:
2020, Professor Niels Schaft, Medicine (MD thesis on T cell immunotherapy), University of Erlangen, Germany
Habilitation:
2024, University Regensburg, “Breaking barriers to CAR T cell therapy”
Principal investigator:
Since 2022, with Prof. Luca Gattinoni, CRC TRR 221 (subproject A07)
Clinician Scientist:
Since 2021, Else Kröner Clinician Scientist Program at Regensburg University (supervisor: Prof. Hinrich Abken)
Resident & Postdoc:
Since 2019, Dept. of Internal Medicine III – Hematology and Oncology, Regensburg
Supplementary Career Information
Not applicable.
Activities in the Research System
- 2024, University Regensburg, Habilitation: “Breaking barriers to CAR T cell therapy”
- Regular involvement in teaching (hematology and molecular medicine)
Supervision of Researchers in Early Career Phases
- Gabriele Inchingolo – PhD thesis (Ongoing)
- Matthias Eder – MD thesis (Ongoing)
Scientific Results
Category A
- Harrer DC, Schlierkamp-Voosen T, Barden M, Pan H, Xydia M, Herr W, Dörrie J, Schaft N, Abken H. Chimeric Antigen Receptor (CAR) T Cells Releasing Soluble SLAMF6 Isoform 2 Gain Superior Anti-Cancer Cell Functionality in an Auto-Stimulatory Fashion. Cells. 2025; Jun 14;14(12):901.
- Harrer DC, Eder M, Barden M, Pan H, Herr W, Abken H. Ectopic PU.1 Expression Provides Chimeric Antigen Receptor (CAR) T Cells with Innate Cell Capacities Including IFN-β Release. Cancers 2024; 16, 2737.
- Harrer DC, Li SS, Kaljanac M, Bezler V, Barden M, Pan H, Herr W, Abken H. Magnetic CAR T cell purification using an anti-G4S linker antibody. J Immunol Methods 2024; May; 528:113667.
- Harrer DC, Li SS, Kaljanac M, Barden M, Pan H, Abken H. Fine-tuning the antigen sensitivity of CAR T cells: emerging strategies and current challenges. Front Immunol 2023; Nov 27;14:1321596.
- Harrer DC, Bezler V, Hartley J, Herr W, Abken H. IRF4 downregulation improves sensitivity and endurance of CAR T cell functional capacities. Front Immunol 2023; May 23; 14:1185618.
- Harrer DC, Schenkel C, Bezler V, Kaljanac M, Hartley J, Barden M, Pan H, Holzinger A, Herr W, Abken H. CAR Triggered Release of Type-1 Interferon Limits CAR T-Cell Activities by an Artificial Negative Autocrine Loop. Cells 2022; 30;11(23):3839.
- Harrer DC, Schenkel C, Berking C, Herr W, Abken H, Dörrie J, Schaft N. Decitabine-Mediated Upregulation of CSPG4 in Ovarian Carcinoma Cells Enables Targeting by CSPG4-Specific CAR-T Cells. Cancers (Basel) 2022; 14;14(20):5033.
- Harrer DC, Heidenreich M, Fante MA, Müller V, Haehnel V, Offner R, Burkhardt R, Herr W, Edinger M, Wolff D, Thomas S, Brosig A. Apheresis for chimeric antigen receptor T-cell production in adult lymphoma patients. Transfusion 2022; 62(8):1602-1611.
- Harrer DC, Schuler G, Dörrie J, Schaft N. CSPG4-Specific CAR T Cells for High-Risk Childhood B Cell Precursor Leukemia. Int J Mol Sci 2019; 20,2764.
- Harrer DC*, Simon B*, Fujii SI, Shimizu K, Uslu U, Schuler G, Gerer KF, Hoyer S, Dörrie J, Schaft N. RNA-transfection of γ/δ T cells with a chimeric antigen receptor or an α/β T-cell receptor: a safer alternative to genetically engineered α/β T cells for the immunotherapy of melanoma. BMC Cancer 2017;17:551.
Category B
- Harrer, D.C., Abken, H. Immuntherapie mit CAR-T-Zellen: der Durchbruch in der Krebsbehandlung. In: Fehse, B., Schickl, H., Bartfeld, S., Zenke, M. (eds) Gen- und Zelltherapie 2.023 - Forschung, klinische Anwendung und Gesellschaft. Springer, Berlin, Heidelberg 2023; https://doi.org/10.1007/978-3-662-67908-1_10.
Academic Distinctions
- 2024 – Sander Foundation Research Grant
- 2024 – Helga-Reifert Award for cancer research
- 2024 – BZKF – Young Scientist Fellowship
- 2021–2023 – Else Kröner Fresenius Foundation (“Erstantragsteller Programm”)
- 2020 – ReForM A (intramural funding) grant of Medical Faculty
- 2020 – Gerok scholar within the CRC TRR 221
Contact to Principal Investigators
Dr. med. Dennis Harrer
Universitätsklinikum Regensburg
Klinik und Poliklinik für Innere Medizin III
Franz-Josef-Strauß-Allee 11
93053 Regensburg
T: +49 941 944-15557
dennis.harrer(at)ukr.de
Prof. Dr. med. Luca Gattinoni
LIT – Leibniz Institute for Immunotherapy (former RCI)
c/o Universitätsklinikum Regensburg
Franz-Josef-Strauß-Allee 11
93053 Regensburg
T: +49 941 944-38131
luca.gattinoni(at)ukr.de
