Because the IGLV3-21-R110 mutation occurs exclusively on CLL cells and not on healthy B cells, it represents an ideal tumor-specific target. Current immunotherapies such as CAR T cells and bispecific antibodies typically attack broadly expressed B-cell antigens like CD19 or CD20, leading to depletion of both malignant and healthy B cells. While effective for some patients, this approach can be problematic in high-risk CLL, where responses remain limited.

Lead by Prof. Dr. Mascha Binder, researchers at the Department of Biomedicine, have now developed a new immunotherapeutic strategy designed to address this clinical need. Their findings, published in Haematologica, demonstrate that a bispecific antibody (BiTE) targeting IGLV3-21-R110 can effectively redirect T cells against leukemia cells carrying this mutation.

The antibody was tested in preclinical models using patient-derived samples and showed efficient T cell activation, cytokine release and triggered robust killing of IGLV3-21-R110–positive CLL cells. Importantly, the antibody spared IGLV3-21 wild-type cells, underlining the mutation specificity and safety potential of the approach.

This work opens the door to mutation-directed immunotherapy in CLL, expanding the concept of precision oncology to include antibody-based therapies.

These findings highlight a promising path forward for developing targeted treatments tailored to genetic risk profiles in CLL. While further clinical testing is required, the data suggest that mutation-specific bispecific antibodies may complement existing therapies and improve outcomes for this difficult-to-treat patient group.

We congratulate Claudia Fischer, and their colleagues on this important contribution to the field of hematology and immunotherapy.

Original Publication