Fc Gamma R

Monoclonal IgG antibodies targeting tumor antigens and receptors, such as CD20 (rituximab), erbB-2 (trastuzumab), and epidermal growth factor receptor (cetuximab), have shown remarkable activity in the clinic against a wide range of malignancies and are now part of standard treatment protocols. The activity of IgG antibodies is regulated in part by a diverse family of Fc gamma receptors (Fc?R), which bind to the constant Fc region of IgG antibodies. Fc?R are expressed on various cell types of hematopoietic origin, thus linking the diversity and specificity of antibodies to various immunological activities. Many of the antibodies used in the clinic activate Fc?R on macrophages and NK cells, leading to tumor cell phagocytosis and lysis. More recent data have also highlighted the involvement of the Fc?R system in potentiating chronic inflammation and de novo carcinogenesis and have also suggested that polymorphisms in FCGR genes can influence the outcome of antibody therapy. Fc?R biology is complex, owing to the expression of multiple Fc?R classes in overlapping expression patterns, all of which differ in their capacity to bind to various antibody isotypes. Nonetheless, a more complete understanding of Fc?R biology is beginning to emerge, which will help guide the development of the next generation of antibody therapies.