Two Are Better than One: The Bi-Specific Antibody Mosunetuzumab Reveals an Improved Immune Response of Vγ9Vδ2 T Cells Targeting CD20 in Malignant B Cells in Comparison to the Mono-Specific Antibody Obinutuzumab.

In treating cancer, immunotherapy has been established as a later-line treatment option in clinical practice. That includes stem cell transplantation, modified or activated immune cells, and antibodies directed against aberrant cells. As an unconventional immune cell subgroup, γδ T cells have been shown to provide effects against malignant cells. They exhibit an MHC-independent activation process, which could diminish graft-versus-host disease after an adoptive transfer of allogeneic cells. Over the last years, the efficacy of therapeutic antibodies has been improved. As a bi-specific antibody, mosunetuzumab binds to both CD3 and CD20, thereby providing close proximity between effector and target cells. Here, we set out to analyze the efficiency of γδ T cells' anti-tumor effects in combination with mosunetuzumab vs. the monoclonal anti-CD20 antibody obinutuzumab. Mosunetuzumab revealed improved responses of γδ T cells regarding their expression of IFN-γ and CD107a and their cytotoxicity towards malignant B cells from lymphoma B cell lines. In comparison to obinutuzumab, mosunetuzumab led to an equivalent or enhanced cytotoxicity against B cell lymphoma cell lines and primary patient samples, where this effect was even more prominent. In summary, we consider the combination of stimulated γδ T cells and mosunetuzumab to be a promising therapeutic approach for future clinical trials.