Therapeutically modified white blood cells hold great potential in the treatment of multiple myeloma, a malignant cancer of the bone marrow. However, they can lead to serious resistance in treated patients. Medical doctors and scientists from the University Hospital and the Helmholtz Institute for RNA-based Infection Research have now uncovered a crucial resistance mechanism.
In the process, they uncovered a crucial resistance mechanism. The results were just published in the journal Nature Medicine. Multiple myeloma is a malignant cancer of the bone marrow. A great hope in the fight against the so far incurable disease rests on new immunotherapies, in particular on the treatment with CAR-T cells.
T cells are white blood cells that serve the immune defense. In their natural state, they are mostly "blind" to tumor cells. However, they can be genetically modified to detect — as CAR-T cells — specific target antigens, i.
The treatment response was quite spectacular: Within a very short time, the bone marrow seemed to be completely cleared of tumor cells, and the myeloma indicators in the patient's blood also fell below the detection limit. However, this was only a temporary victory. After five months, there was a massive relapse: the bone marrow was again flooded with myeloma cells, and the patient died within a few weeks.
To track down this initially unexplained loss, HIRI scientists analyzed the genome of thousands of the myeloma cells in question by single-cell RNA ribonucleic acid sequencing. The researchers believe that selection induced by CAR-T cell therapy is behind this. While the cells with BCMA were successfully tracked down and eliminated, the remaining cells without BCMA had such a survival advantage that they subsequently grew rapidly.
