Researchers at the Max Delbrück Center have developed an optimized CAR-T cell therapy against multiple myeloma. The highlight: The modified immune cells recognize degenerated plasma cells simultaneously by two surface features – BCMA and BAFF-R – and destroy them more reliably.

Multiple myeloma is an incurable cancer of the bone marrow in which plasma cells proliferate uncontrollably and produce antibodies. The disease destroys bones and causes severe pain. Conventional chemotherapies and antibody therapies as well as stem cell transplants improve the prognosis only to a limited extent.

CAR-T cell therapies, which have been approved for several years, are significantly extending the lives of many patients. In this process, the patient’s own T cells are removed, genetically equipped with a chimeric antigen receptor (CAR) that recognizes the protein BCMA on myeloma cells, and infused back. BCMA occurs almost exclusively on plasma cells.

However, the protein is completely absent in some patients or is lost in the course of therapy. This leads to resistance to therapy or recurrence, which often ends fatally.

The team led by Dr. Armin Rehm and PD Dr. Uta Elisabeth Höpken used single-cell RNA sequencing, immunohistochemistry and flow cytometry to identify the BAFF receptor as the second typical feature of malignant plasma cells. BAFF-R is particularly abundant on recurrent cells and BCMA-negative myeloma cells.

The bispecific CAR-T cells developed dock onto both receptors. In experiments with myeloma cell lines and the patient’s own bone marrow cells, they remained effective even when BCMA was missing or lost.

About 5 to 30 percent of patients could benefit from the approach. Screening before the start of therapy is intended to identify suitable candidates.

The team is planning a clinical trial in cooperation with the National Center for Tumor Diseases (NCT). Researchers from Charité – Universitätsmedizin Berlin and Universitätsmedizin Greifswald were also involved.

The results were published in Molecular Therapy.

Original Paper:

Agnese Fiori, et al. (2025): “Bispecific BAFF-R/BCMA CAR T cells control growth of
heterogeneous plasma cells in multiple myeloma”. Molecular Therapy, DOI: 10.1016/j.ymthe.2025.12.005

Editor: X-Press Journalistenbüro GbR

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