Biomarkers for the successful treatment of tumors in the bone marrow identified

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CAR-T cell therapy has been established as an effective treatment for various haematological cancers. However, the treatment does not have the same level of success in all patients. In a current clinical study, researchers from the University of Leipzig Medical Center and the Fraunhofer Institute for Cell Therapy and Immunology IZI have identified various biomarkers which are linked to the response to CAR-T cell therapy in multiple myeloma, a type of bone marrow cancer. The results of their study were published in the renowned journal Nature Cancer.

Since the first approvals in 2017/2018, CAR-T cell therapy has become established as an effective therapeutic option for various haematological cancers. For this treatment, immune cells, the so-called T cells, are harvested from the patients and genetically modified in the laboratory so that they carry a receptor on their surface with which they can detect the cancer cells and initiate their destruction. In spite of impressive clinical successes, however, a proportion of patients do not respond to this treatment. Now, for the first time, researchers of Fraunhofer IZI and the University of Leipzig Medical Center have succeeded in identifying biomarkers correlating with successful treatment.

To achieve this, immune cells were isolated from the blood of multiple myeloma patients, before and after treatment with an approved CAR-T cell therapy. These cells were then examined in a so-called single-cell multiomics analysis. As a result, various parameters of all cells examined could be recorded and analysed. These parameters included the transcriptome, sequences of T and B cell receptors, as well as selected surface markers. The data obtained were then analysed using bioinformatics at Fraunhofer IZI and, as a result, information was gained on the functional condition of individual cells, on how they differ and how they interact with each other. For example, one finding was that patients who did not respond to CAR-T cell treatment for the most part had an immunosuppressant microenvironment at the time of apheresis.

These results do not only provide a possible explanation for the causes of the therapy resistance; they can also support treatment decisions in future and indicate options for the continued improvement of CAR-T cell therapy. 

In addition, the results are also integrated into CERTAINTY, an EU project coordinated by Fraunhofer IZI, which aims to develop a virtual twin for improved treatment plans using CAR-T cells in multiple myeloma.

Publication in Nature Cancer: Single-cell multiomic dissection of response and resistance to chimeric antigen receptor T cells against BCMA in relapsed multiple myeloma. DOI: 10.1038/s43018-024-00763-8.