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

双特异性抗体Mosunetuzumab优于单特异性抗体Obinutuzumab:与单特异性抗体Obinutuzumab相比,双特异性抗体Mosunetuzumab可增强靶向恶性B细胞中CD20的Vγ9Vδ2 T细胞的免疫反应。

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Abstract

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.

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