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In a study led by the University of Leipzig Medical Center and the Fraunhofer IZI, researchers have examined how two innovative CAR T-cell therapies targeting the B-cell maturation antigen perform in patients with hard-to-treat multiple myeloma. Their aim was to determine which molecular mechanisms influence the therapeutic success of such living, cell-based therapies in this blood cancer. The findings have been published in the renowned journal Cancer Cell. The Leipzig research team led by Professor Maximilian Merz and Dr Kristin Reiche has now secured a further two million euros in funding for a new project to advance the development of next-generation immunotherapies for multiple myeloma.
In multiple myeloma, plasma cells proliferate uncontrollably in the bone marrow, disrupting the growth of healthy blood-forming cells. If the disease recurs after treatment or fails to respond, CAR T-cell therapy may be considered. In this innovative and personalised form of cancer immunotherapy, immune cells (T cells) are taken from the patient and genetically modified in the laboratory to enhance their ability to recognise and attack cancer cells. The modified autologous cells (CAR T cells) are then reinfused into the patient. Once active in the body, they seek out and destroy malignant cells.
A research team led by Leipzig University Medical Center and the Fraunhofer Institute for Cell Therapy and Immunology IZI has examined in greater detail how such living, cell-based therapies act in the body over an extended period. The researchers analysed two CAR T-cell therapies directed against the B-cell maturation antigen (BCMA). BCMA is present on the surface of malignant plasma cells and is therefore a suitable target for therapeutic approaches.
The study involved 61 patients: 34 received CAR T-cell therapy with idecabtagene vicleucel (ide-cel) and 27 were treated with ciltacabtagene autoleucel (cilta-cel). Treatment with cilta-cel led to complete remission in a substantially higher proportion of patients – 78 per cent compared with 38 per cent for ide-cel. It was also associated with longer progression-free survival, meaning that disease control was maintained for a longer period.
Professor Maximilian Merz, who led the study in his role as senior physician and head of the Multiple Myeloma Unit at the University of Leipzig Medical Center, emphasises: “Such insights are highly important for patient care. We were able to show that tumour burden, T-cell fitness and overall systemic inflammation play a major role in determining the success of CAR T-cell therapy.”
The reasons for the improved efficacy and the differing side-effect profiles of the two products are still poorly understood. The project team at the University of Leipzig Medical Center and the Fraunhofer IZI therefore carried out single-cell multi-omics analyses on a total of 135 blood samples. Such investigations make it possible to capture the molecular characteristics of individual cells over an extended period and to track cellular changes in detail. The analyses showed that treatment with cilta-cel induces the expansion of certain immune cells that are important for combating cancer but can also give rise to side effects.
Dr Kristin Reiche, head of the Department of Medical Bioinformatics at the Fraunhofer IZI, explains: “The pharmacokinetics – in other words, how the human body interacts with the two CAR T-cell therapies – differ. Cilta-cel exhibits a delayed onset of expansion but reaches higher cell numbers overall, meaning that CAR T cells proliferate more slowly at first but ultimately more extensively. For this reason, cytokine release syndrome, a possible side effect of the therapy, may also occur later.”
Further study – two million euros in funding for research
The successful collaboration between the two lead institutions, the University of Leipzig Medical Center and Fraunhofer IZI, has now resulted in a follow-up project receiving more than two million euros in funding from the Hector Foundation.
In addition to CAR-T cell therapies, bispecific antibodies have also revolutionised the treatment of multiple myeloma in recent years – three of the four bispecific antibodies currently approved in Germany likewise target the surface molecule BCMA. However, the two therapeutic approaches work in different ways, exhibit distinct pharmacokinetic properties and are currently used without a clearly defined treatment sequence. In this new project, the researchers aim to use comprehensive multi-omics analyses of samples from relapsed myeloma patients to investigate how CAR-T cells and bispecific antibodies might be optimally combined or aligned with one another in future.
Translation: Matthew Rockey
Press Office, Faculty of Medicine, Leipzig University
presse-mf@medizin.uni-leipzig.de
Original publication in Cancer Cell: A longitudinal single-cell atlas to predict outcome and toxicity after BCMA-directed CAR T cell therapy in multiple myeloma. DOI: https://doi.org/10.1016/j.ccell.2025.10.014
In the study, researchers from Leipzig investigated the molecular mechanisms of two CAR-T cell thera ...
Copyright: Colourbox
Prof. Dr. Maximilian Merz
Copyright: Memorial Sloan Kettering Cancer Center (MSKCC)
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In the study, researchers from Leipzig investigated the molecular mechanisms of two CAR-T cell thera ...
Copyright: Colourbox
Prof. Dr. Maximilian Merz
Copyright: Memorial Sloan Kettering Cancer Center (MSKCC)
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