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CD20+/CD47+ B-cell lymphoma cells are malignant B-lymphocytes characterized by the simultaneous expression of the B-cell lineage marker CD20 and the immune-evasive "don't eat me" signal CD47. CD20 (MS4A1) is a 33-37 kDa non-glycosylated phosphoprotein that plays a role in B-cell development and calcium channel modulation, serving as a classic target for monoclonal antibodies like rituximab (UniProt P11836). CD47 is a transmembrane protein that acts as a ligand for Signal Regulatory Protein Alpha (SIRPα) on macrophages, delivering an inhibitory signal that prevents phagocytosis (UniProt Q08722). In B-cell lymphomas, the overexpression of CD47 allows tumor cells to evade innate immune surveillance even in the presence of pro-phagocytic signals. Therapeutic strategies targeting these cells, such as bispecific antibodies (e.g., IMM0306, TG-1801), leverage CD20 for tissue specificity while blocking CD47 to restore macrophage-mediated tumor clearance. This dual-targeting approach aims to maximize anti-tumor efficacy through enhanced antibody-dependent cellular phagocytosis (ADCP) while minimizing systemic toxicity, such as hemagglutination or anemia, by preferentially targeting cells that express both markers.
Simultaneous binding to CD20 and CD47 on the surface of B-cell lymphoma cells. CD20 binding provides specificity for the B-cell lineage, while CD47 blockade disrupts the inhibitory CD47-SIRPα interaction with macrophages. This dual engagement promotes antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) by neutralizing the "don't eat me" signal and recruiting immune effector cells to the tumor site.
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