Low affinity immunoglobulin gamma Fc receptor III (CD16) (CD16)

The Fc gamma receptor III (CD16) is a cluster of differentiation molecule found on the surface of various immune cells, including natural killer (NK) cells, neutrophils, and macrophages. It exists in two isoforms: CD16a (FCGR3A), a transmembrane protein primarily on NK cells and monocytes that triggers antibody-dependent cellular cytotoxicity (ADCC), and CD16b (FCGR3B), a GPI-anchored protein expressed on neutrophils. CD16 binds with low affinity to the Fc portion of IgG antibodies, acting as a critical bridge between the adaptive and innate immune systems by sensing opsonized pathogens or tumor cells. [Source: UniProt P08637, NCBI Gene 2214]. In clinical practice, CD16 is a primary target for enhancing the efficacy of monoclonal antibodies. Many oncology drugs, such as Rituximab and Trastuzumab, rely on CD16-mediated ADCC to eliminate cancer cells. A well-known genetic polymorphism (V158F) in the FCGR3A gene significantly impacts the binding affinity of IgG1 and determines the clinical response to various antibody therapies. [Source: PubMed PMID: 10656158]. Emerging therapies, including bispecific innate cell engagers, specifically target CD16 to bypass traditional antibody limitations and directly recruit NK cells to the tumor microenvironment. [Source: StatPearls - NK cells].

Other names

Fc gamma receptor IIIFc-gamma RIIIFCGR3FCGR3AFCGR3BCD16aCD16bIGFR3

CD16 serves as a key mediator for antibody-dependent cellular cytotoxicity (ADCC) by binding the Fc region of IgG antibodies. Therapeutic antibodies utilize this interaction to recruit Natural Killer (NK) cells and macrophages to lyse target cells. Bispecific engagers (e.g., AFM13) simultaneously bind CD16 on immune effectors and specific antigens on tumor cells to bridge and activate the immune response.