A novel anti-CD20, concabody, enhances immunotherapy efficacy by targeting MPZL1 and augmenting antibody-induced cell death

Introduction: While anti-CD20 antibodies like obinutuzumab (OBI) have improved clinical outcomes, B-cell malignancies remain a significant therapeutic challenge. OBI induces direct cell death (DCD) and augments antibody-dependent cellular cytotoxicity (ADCC), but the molecular mechanisms involved in DCD remain unclear. This study aims to bridge this knowledge gap and develop enhanced treatment modalities. Methods: experiments using peripheral blood mononuclear cells (PBMCs) from patients with chronic lymphocytic leukemia (CLL). Results: mutant, and the concabodies efficiently depleted malignant B cells in CLL patient samples. Discussion: Taken together, this work establishes MPZL1 as a crucial molecular target for antibody-induced DCD and presents concabodies as a mechanistically rational and clinically relevant approach to improve the efficacy of anti-CD20 immunotherapy in B-cell malignancies.