CD20-targeted immunotherapies in B-cell malignancies: mechanistic and clinical advances

Over the past two decades, targeted immunotherapies have significantly transformed the treatment landscape for CD20-positive B-cell hematological malignancies, including non-Hodgkin lymphoma and chronic lymphocytic leukemia. The substantial clinical benefits of rituximab administration have made CD20 a central therapeutic target, paving the way for next-generation modalities, such as antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T cells, which have markedly improved clinical response rates, particularly in relapsed or refractory disease. These advances are underpinned by genetically engineered approaches that enhance antigen specificity and cytotoxic potency by appropriately activating the immune system while attenuating associated adverse effects. This review examines the structural characteristics and clinical outcomes of current Food and Drug Administration-approved and investigational CD20-targeted therapies. Moreover, the key resistance mechanisms and new strategies to circumvent them, including the use of targeted drug combinations and patient selection based on predictive biomarkers, were highlighted.