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Overview:
MacroGenics is using state of the art genetic engineering methodology to exploit the biological significance of Fc-receptors [CD16 (FcRIII) and CD32B (FcRIIB)] in autoimmunity and cancer. In autoimmune diseases such as systematic lupus erythematosis, antibodies to self antigens cause cellular pathology and inflammation through the interaction of the Fc segment with specific receptors on effector cells. MacroGenics' product candidates (anti-CD16 and soluble FcRs) are novel inhibitors of CD16 function for preventing the damage caused by such autoantibodies. Similarly, antibodies against CD32B (the inhibitory receptor) are being developed for cancer, autoimmune and allergy applications.
The same FcR interactions are involved in the destruction of tumor cells by anti-tumor antibodies. In order to make such antibodies more potent, we have generated variant Fc segments with modified affinities for the different activating (CD16) and inhibitory (CD32B) FcRs. These improved Fc segments will be utilized in monoclonal antibodies for newly identified or existing tumor targets.
MacroGenics utilizes mice expressing human rather than mouse Fc receptors in models of autoimmunity and cancer. The evaluation of Fc modified antibodies in vivo has been facilitated by the construction of mouse lines in which the murine Fc receptors have been deleted and human transgenes expressing human FcRs have been introduced. These novel mouse strains accurately reflect the complexity of the human FcR system by faithfully reproducing the pattern of expression of the human activation and inhibitory receptor genes, which differ from the murine pattern.
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