Fontolizumab Overview

Introduction of Fontolizumab

Fontolizumab (planned trade name HuZAF), the form of a murine antihuman, is a humanized monoclonal antibody by using recombinant technology. As well as, it is an immunosuppressive drug for the treatment of auto-immune diseases like Crohn's disease. It was discovered and developed by Protein Design Labs, Inc., Fremont, California, USA. This monoclonal antibody was designed to bind and neutralize interferon gamma (IFN-γ). It also was used in a phase II clinical trial investigating the use for rheumatoid arthritis, but the clinical trial was terminated because the first phase did not meet the endpoint. Although, fontolizumab was generally well tolerated and minimally immunogenic in patients with moderate to severe CD. Biological and clinical responses were evident in patients treated with single dose fontolizumab and in multiple dose maintenance of remission. Unfortunately, the drug currently has not obtained encouraging clinical trial results. clinical trial results.

Mechanism of Action of Fontolizumab

Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any part of the gastrointestinal tract from mouth to anus. Signs and symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever and weight loss. While the cause of Crohn's disease is unknown, it is believed to be due to a combination of environmental, immune and bacterial factors in genetically susceptible individuals. It results in a chronic inflammatory disorder, in which the body's immune system attacks the gastrointestinal tract possibly directed at microbial antigens. There are no medications or surgical procedures that can cure Crohn's disease. In IBD, many immunoregulatory abnormalities in intestinal and peripheral T lymphocytes are noted. This includes, for instance, the altered ratio of proinflammatory to immunosuppressive cytokines, the selective activation of T-helper lymphocyte subsets and abnormalities in epithelial antigen presentation. In Crohn disease, there is a chronic T helper 1 (Th1)-driven immune response with overproduction of inflammatory cytokines, such as IFN-γ and interleukin (IL). Interferon γ (IFN-γ), a type II interferon, is one of the most potent and pleiotropic cytokines, exhibiting a multitude of immunoregulatory functions. IFN-γ can activate a wide range of immunocompetent cell types, including macrophages, endothelial cells, and lymphocytes, and is a key factor for expression of class II MHC molecules on antigen presenting cells. In addition, IFN-γ decreases epithelial barrier function and promotes neutrophil migration by increased expression of chemokines and their receptors. Therefore, IFN-γ seems to be one of the key cytokines during intestinal inflammation. IFN-γ can induce tight junction reorganization and/or epithelial damage that causes a leaky mucosal barrier. In health, a polarized monolayer of columnar intestinal epithelial cells normally forms a tight barrier to the access of toxic agents to the mucosal immune system. However, IFN-γ disrupts tight junctions and thereby disturbs paracellular transport mechanisms. Fontolizumab is the humanized form of a murine antihuman IFN-γ antibody derived by using recombinant technology. The antibody binds to natural human IFN-γ and inhibits expression of IFN-γ regulated genes known to be upregulated in Crohn's disease.

Fig 1. Mechanism of Action of Fontolizumab

What We Provide

Therapeutic Antibody

Fontolizumab

We provide high-quality Fontolizumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

For research use only. Not intended for any clinical use.