Journal
MABS
Volume 3, Issue 1, Pages 49-60Publisher
LANDES BIOSCIENCE
DOI: 10.4161/mabs.3.1.13989
Keywords
IL-1 beta; gevokizumab; gout; inflammation; autoimmune disease; affinity; therapeutic antibody
Categories
Ask authors/readers for more resources
Interleukin-1 beta (IL-1 beta) is a potent mediator of inflammatory responses and plays a role in the differentiation of a number of lymphoid cells. In several inflammatory and autoimmune diseases, serum levels of IL-1 beta are elevated and correlate with disease development and severity. The central role of the IL-1 pathway in several diseases has been validated by inhibitors currently in clinical development or approved by the FDA. However, the need to effectively modulate IL-1 beta-mediated local inflammation with the systemic delivery of an efficacious, safe and convenient drug still exists. To meet these challenges, we developed XOMA 052 (gevokizumab), a potent anti-IL-1 beta neutralizing antibody that was designed in silico and humanized using Human Engineering (TM) technology. XOMA 052 has a 300 femtomolar binding affinity for human IL-1 beta and an in vitro potency in the low picomolar range. XOMA 052 binds to a unique IL-1 beta epitope where residues critical for binding have been identified. We have previously reported that XOMA 052 is efficacious in vivo in a diet induced obesity mouse model thought to be driven by low levels of chronic inflammation. We report here that XOMA 052 also reduces acute inflammation in vivo, neutralizing the effect of exogenously administered human IL-1 beta and blocking peritonitis in a mouse model of acute gout. Based on its high potency, novel mechanism of action, long half-life and high affinity, XOMA 052 provides a new strategy for the treatment of a number of inflammatory, autoimmune and metabolic diseases in which the role of IL-1 beta is central to pathogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available