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Biomarkers Linked to Cell Therapy Response for Bone Marrow Tumors Identified

Cancer cells.
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CAR T cell therapy involves the collection of immune cells called T cells from the patient. These are genetically modified in the laboratory to carry a receptor on their surface. This receptor enables the immune cell to recognise the cancer cells and initiate their destruction. Despite impressive clinical results, some patients do not respond to CAR T cell therapy. For the first time, a team led by researchers at the University of Leipzig Medical Center has identified biomarkers associated with the success of this therapy in multiple myeloma.

“Using state-of-the-art single-cell sequencing, we can now predict whether patients will respond well or less well to CAR T cell therapy before treatment begins,” says PD Dr Maximilian Merz, corresponding author of the recent study from the University of Leipzig Medical Center. The researchers were also able to show that the normal immune system learns from the CAR T cells how to destroy myeloma cells, which are responsible for malignant growths in the bone marrow.

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In the clinical study, blood and bone marrow samples from patients with multiple myeloma were taken before and after infusion of CAR T cells and analysed for certain biomarkers. To do this, the cells were subjected to fluorescence-activated cell analysis. The researchers also characterised gene expression, T and B cell receptors and surface proteins at the single cell level.

Based on the new data, a follow-up project will use this complex method to analyse more patients with multiple myeloma who have received CAR T cell therapy. “The aim is to identify the right time for CAR T cell therapy in multiple myeloma at an early stage,” says PD Dr Merz, Senior Physician at the Department for Hematology, Cell Therapy and Hemostaseology at the University of Leipzig Medical Center. In addition, as part of the major international CERTAINTY project, funded with around ten million euros, there are plans to develop a virtual twin to improve treatment planning for CAR T cells in multiple myeloma.

Reference: Rade M, Grieb N, Weiss R, et al. Single-cell multiomic dissection of response and resistance to chimeric antigen receptor T cells against BCMA in relapsed multiple myeloma. Nat Cancer. 2024. doi: 10.1038/s43018-024-00763-8

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