Low affinity immunoglobulin gamma Fc receptor IIIa (CD16a) and B-lymphocyte antigen CD19 (CD16a/CD19)

The interaction between CD16 (FCGR3A) on natural killer (NK) cells and CD19 on B-cell tumor cells, mediated by anti-CD19 antibodies, is a critical mechanism for treating B-cell malignancies. CD19 is a transmembrane protein universally expressed on B-cells and is a hallmark target for leukemias and lymphomas (UniProt P15391). CD16a is a low-affinity Fc receptor found on NK cells that, when engaged by the Fc portion of an antibody, triggers antibody-dependent cellular cytotoxicity (ADCC) (UniProt P08637). Therapeutic antibodies like tafasitamab are engineered to have an enhanced affinity for CD16a, thereby strengthening the bridge between the effector NK cell and the CD19-positive tumor cell (Salles et al., 2020). This engagement leads to the release of perforins and granzymes, resulting in the targeted lysis of the malignant B-cell. This strategy is particularly effective in non-Hodgkin lymphoma and other B-cell proliferative disorders where CD19 is highly expressed. Safety concerns primarily involve B-cell depletion and infusion-related reactions, which are common to many B-cell targeting therapies (FDA Label: Monjuvi).

Other names

FCGR3ACD16CD19B-cell surface antigen B4Fc-gamma RIIIaT-cell surface glycoprotein CD16aCD16a-CD19 axis

Antibody-dependent cellular cytotoxicity (ADCC) mediated by the recruitment of CD16-positive natural killer (NK) cells to CD19-positive tumor cells via an anti-CD19 antibody bridge.