Abstract

Dysregulated B cells are central to many hematologic malignancies and autoimmune diseases, but current B cell–targeted therapies often fail to translate binding into effective signaling. Here, we present CD20 EryPatch, a living dynamic cellular patch that co-opts natural erythrocyte processes of morphological and biological changes, enabling a dual mechanism of micrometer-scale mechanotransduction and phagocytic “tag-and-clear” for enhanced B cell depletion. CD20 EryPatches are designed to adhere to B cells and anchor on CD20 receptors across extensive cell surface areas. Their progressive discocyte-to-echinocyte transition provides deformability-driven traction, enabling localized, large-scale CD20 cross-linking that amplifies downstream apoptosis in target B cells. Concomitant biomarker alteration on CD20 EryPatch converts it into an “eat me” tag attached to the B cell, facilitating further clearance by initiating erythrophagocytosis. This approach proves more effective than standard CD20 monoclonal antibodies in models of B cell disorders, including non-Hodgkin lymphoma, systemic lupus erythematosus, and rheumatoid arthritis.