Cytotoxic Fc Domains

Xencor’s high cytotoxicity (antibody-dependent cellular cytotoxicity, ADCC) XmAb Fc domain technology is designed to improve the immune system’s elimination of tumor and other pathologic cells.

This Fc domain has two amino acid changes, resulting in a 40-fold greater affinity for FcγRIIIa, the receptor that activates Natural Killer (NK) cells to destroy cancer cells and foreign pathogens. FcγRIIIa is considered an important mediator of the antitumor efficacy of antibodies such as trastuzumab (marketed as Herceptin by Genentech/Roche) and rituximab (marketed as Rituxan by Genentech/Roche). Xencor has applied its high ADCC Fc domain to a large number of antibodies and in all cases demonstrated a marked increase of ADCC measured in vitro.

It also increases affinity for FcγRIIa, with potential for recruitment of other effector cells such as macrophages, which play a role in immunity by engulfing and digesting foreign material.

Our Cytotoxic Fc domain is used in four partnered clinical-stage programs, two in Phase 2 and two in Phase 1 testing.