Xencor is working to improve antibody immune function, potency, affinity and ease of production through engineering its suite of Fc and Fv domains with its XmAb technology. The Monrovia, CA-based company has substantially extended the half-life of its antibodies, offering the potential to reduce their overall cost.
The Fc domain binds to different activating and inhibitory receptors on immune effector cells. The former help build a response to the targeted disease, and the latter help keep the immune reaction from being overactivated.
"Human restringing" is a key part of the company's Fv (variable) domain technology. The process selects the best human sequence components that match the structure of an antibody.
The company's XmAb5871, licensed by Amgen in January 2011, is in Phase I trials for autoimmune diseases. The antibody targets the antigen CD19 and "co-engages" CD32B.
Preclinical studies published in the Journal of Immunology show that XmAb5871 suppresses autoimmune responses in humanized mouse models of lupus. This indicates that XmAb5871 could be effective in multiple autoimmune indications, including lupus and rheumatoid arthritis. The antibody does not deplete B cells, which has caused serious safety issues in other antibody therapies targeting autoimmune disorders because they stymie healthy immunity to infection.
Xencor's XmAb engineering also creates more tumor-killing power by increasing antibodies' ability to get the body's immune system to target cancer cells. And the company's lead compound, XmAb2513, targets the antigen CD30. XmAb2513 has completed Phase I trials for Hodgkin's lymphoma, where it showed objective tumor responses and was generally well-tolerated by test subjects.