VUB Research points to a new path toward more effective therapy for multiple myeloma

Researchers at the Vrije Universiteit Brussel (VUB) have achieved an important breakthrough in the fight against multiple myeloma, an aggressive form of blood cancer. An international team led by Arne Van der Vreken, Prof. Dr. Eline Menu, and Prof. Dr. Karine Breckpot (Translational Oncology Research Center, VUB) has identified a new therapeutic target that could significantly strengthen existing immunotherapies.

Multiple myeloma, also known as Kahler’s disease, primarily affects older adults and is characterized by the accumulation of malignant plasma cells in the bone marrow. This leads to severe complications such as bone fractures, anemia, infections, and kidney problems. While CAR-T therapy, in which a patient’s own immune cells are genetically engineered to attack cancer cells, has shown great promise in recent years, relapse remains a major challenge. Tumor cells can lose the target protein BCMA, allowing them to escape treatment.

The VUB team has now discovered that another protein, B7-H3, is present on the cancer cells of approximately 60 percent of multiple myeloma patients. This had never been described before for this blood cancer. B7-H3 therefore represents a new and important therapeutic target.

This discovery was made possible through close collaboration with the University Hospital of Parma and UZ Brussels, which provided access to an exceptionally rich biobank of patient samples. This allowed the researchers to analyze B7-H3 expression directly in real patient cells, rather than only in cell lines, and to map the substantial heterogeneity of multiple myeloma tumors.

The team then engineered three types of CAR-T cells:

• CAR-T cells targeting BCMA (the established target),

• CAR-T cells targeting B7-H3 (the newly identified target), and

• dual CAR-T cells capable of recognizing both targets simultaneously.

In mouse models of multiple myeloma, this dual approach produced remarkable results. A single injection of dual CAR-T cells led to complete and sustained elimination of the tumor.

By attacking the cancer on two fronts at once, it becomes far more difficult for tumor cells to evade therapy. This strategy could drastically reduce the risk of relapse, particularly in patients who are not BCMA-positive or whose tumors lose target proteins under treatment pressure.

Although the findings are currently limited to human tissue samples and animal models, they represent a crucial step toward clinical trials in patients. The researchers describe the dual CAR-T strategy as a promising foundation for a new generation of CAR-T therapies with more precise tumor recognition and more durable treatment responses.

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