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Ecto-5'-nucleotidase (CD73) is a cell surface enzyme broadly expressed on subsets of hematopoietic and non-hematopoietic cells, including B lymphocytes[1][2][3][5]. It catalyzes the conversion of extracellular AMP to adenosine, which has immunosuppressive effects via G protein-coupled adenosine receptors (A2AR and A2BR). CD73 is dynamically regulated in B cells: it is predominantly absent on naïve B cells and plasma cells, but highly expressed on germinal center and memory B cells during maturation[2][5]. Besides its enzymatic role, CD73 can function as a costimulatory molecule, influencing lymphocyte activation, migration, and adhesion. Engagement of CD73 on B cells with specific antibodies like mupadolimab leads to robust B cell activation, upregulation of activation and differentiation markers (e.g., CD69, CD83, MHC class II, CD27, CD38), and enhancement of antigen-specific humoral immune responses[1][3]. This activation can be independent of its adenosine-blocking activity and appears unique to certain antibody epitopes[1][3][6]. CD73 plays roles in cancer progression (by fueling immunosuppressive microenvironments)[4][5], inflammation, and infection, making it a promising immunotherapeutic target. Mupadolimab is in clinical development as a cancer immunotherapy and as a vaccine adjuvant. CD73-mediated adenosinergic effects and antibody-induced B cell activation have implications both for anti-tumor and vaccine strategies[1][3][5].
Inhibition of CD73 enzymatic activity (adenosine blockade) Direct activation of B cell maturation and antigen presentation by antibody engagement (unique to mupadolimab) Costimulatory signaling to B lymphocytes
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