Immunotherapies are now established pillars in the treatment of cancer. The principle of CAR-T cell therapy is that the body’s own T cells are programmed to destroy cancer cells through genetic modification. This treatment strategy currently works particularly well for leukemia and lymphoma. In addition to improving the efficacy and safety for these indications, researchers are also working on the development of CAR-T therapies for other types of cancer and for certain autoimmune diseases.
T cells are known to play a central role in the fight against malignant cells. For CAR T cell therapy, the body’s own T cells are removed within a few hours using a procedure similar to blood washing. The cells are then genetically modified in a specially equipped laboratory so that they carry so-called “chimeric antigen receptors” on their surface, which can recognize certain target structures on cancer cells [1]. The term “chimeric” is based on the fact that this biosynthetically produced receptor combines parts of antibodies and T-cell receptors, which does not occur in nature [2]. The CAR-T cells modified in this way are returned to the patient in one of the next steps, as in a blood transfusion. They multiply in the body and fight the cancer cells or misdirected immune cells. This is because the CAR enables the T cells to specifically recognize antigens on (tumour) cells and destroy them by releasing cytotoxic molecules such as granzyme B or perforin [2]. CAR T cells are currently used for the treatment of multiple myeloma, acute B-cell leukemia and various types of lymphoma (diffuse large cell lymphoma, follicular lymphoma, mantle cell lymphoma) [2]. The development of CAR-T cells for use in solid tumors is currently being researched – what still represents a major hurdle in implementation is the targeted transport of CAR into the tumor [3].
| USB study in high-risk chronic lymphocytic leukaemia The T cells modified as part of CAR-T cell therapy recognize and destroy cancer cells in the patient’s body, but unfortunately also healthy blood cells. One aim of current research efforts is to develop more effective and better tolerated treatments. A research group led by Prof. Mascha Binder, Chief Physician for Medical Oncology at the University Hospital Basel (USB) and Prof. Sebastian Kobold, LMU Klinikum München, has succeeded in developing CAR T cells that target these disease-specific mutations in lymphoma with a specific genetic mutation (IGLV3-21R110) – which is associated with a particularly aggressive course – and kill tumor cells highly selectively while sparing healthy cells. This is of great significance for those affected, as patients with this mutation often have limited treatment options and a poorer prognosis. “We are optimistic that this research could represent an important step towards a new type of precision cell therapy and are continuing to collect data on the clinical application of our CAR T cells,” says Prof. Binder. This groundbreaking study was published in the journal Nature Communications in 2024. Initial preparations for a clinical trial are currently underway together with other partners at the University Hospital Basel. |
| to [5,6] |
T2EVOLVE – Project of a multidisciplinary consortium
T2EVOLVE (The Accelerating Development and Improving Access to CAR and TCR-engineered T cell therapy) is a Europe-wide consortium with 27 partners from nine countries [4]. The University Hospital of Würzburg is the lead partner under the direction of Prof. Dr. Michael Hudecek and Prof. Dr. Hermann Einsele. The overarching goal of T2EVOLVE is to accelerate the development of and access to immunotherapy with reprogrammed immune cells. One of the sub-goals is to develop new models and tools that can better predict the efficacy and safety of these therapeutic approaches [4]. Although promising clinical results have been achieved with CAR-T cell therapy and T cells with tumor-specific T cell receptors (TCR-Ts) in the aforementioned hematological cancers, a downer is that severe side effects sometimes occur, such as cytokine release syndrome or neurotoxicities. Another important component of the EU project is the involvement of patients as contributing team members. In order to achieve the ambitious project goals, the promotion of innovation and cooperation as well as the improvement of the state of the art are important concerns of the T2EVOLVE consortium, as Prof. Hudecek, project coordinator and Chair of Cellular Immunotherapy at the University Hospital of Würzbutg, explained [4]. Updated information on the T2EVOLVE project is published at the following web link: https://t2evolve.com.
In Switzerland, too, there are numerous research projects in the field of T-cell therapies, such as a recently published study involving a research group led by Prof. Mascha Binder, Head of Medical Oncology at the University Hospital Basel (USB) [5,6] (box) .
Congress: EHA2024
Literature:
- “New weapon against cancer and autoimmune diseases”, University Hospital and Medical Faculty of the Eberhard Karls University of Tübingen, 19.04.2024.
- Mougiakakos D, Haghikia A: The use of CAR T cells in neuroimmunological diseases, Ärzteblatt Sachsen-Anhalt 11/2024, www.aerzteblatt-sachsen-anhalt.de,(last accessed 12.11.2024).
- “A CAR T-cell chemokine checkpoint accelerator for the treatment of solid tumor cancers (CONAN)”, www.gesundheitsforschung-bmbf.de/de/ein-car-t-zell-chemokin-checkpoint-beschleuniger-fur-die-behandlung-von-soliden-12811.php,(last accessed 12.11.2024).
- “T2EVOLVE – Accelerating Development and Improving Access to CAR and TCR engineered T cell therapy in Europe”, Prof. Dr. med. Michael Hudecek, EHA2024, Madrid, 13.6.-16.6.2024.
- “An important step in personalized medicine against lymphatic cancer”, University Hospital Basel, 08.02.2024.
- Märkl F, et al: Mutation-specific CAR T cells as precision therapy for IGLV3-21R110 expressing high-risk chronic lymphocytic leukemia. Nat Commun 2024 Feb 2; 15(1): 993.
HAUSARZT PRAXIS 2024; 19(11): 19 (published on 22.11.24, ahead of print)
