BIOT 645 Abrilumab Monoclonal Antibody Paper
This concise and articulate report written in prose (600 words) should include the following
MONOCLONAL:” ABRILUMAS ” Source of monoclonal (HUMAN)
Details of the antibody: what is the mechanism of action of this antibody
Commercialization: who is commercializing this antibody? What stage of development is the antibody at? Are any other companies also developing the same antibody? Is there any IP associated with the commercialization?
Manufacturing process: how is the antibody produced? Is it fully-humanized? What kind of yield is required every year? Are there any features which make this antibody difficult to produce in bulk?
Market details: how big is the market for this mAb? Are there multiple markets?
Regulatory details: what kind of regulatory approval is required for this mAb product?
Other applications: are there any other applications for this antibody?
Analysis: what do you think the long-term future of the antibody is? Does it have any other potential applications / indications?
Introduction of Abrilumab
Abrilumab (AMG 181/MEDI 7183) is a fully human monoclonal IgG2 antibody, like vedolizumab, against α4β7 integrin designed for the treatment of inflammatory bowel disease, ulcerative colitis, and Crohn’s disease. Abrilumab was developed by MedImmune, and has been successively approved for marketing in Europe on December 11, 2015.
Mechanism of Action of Abrilumab
The inﬂammatory bowel diseases (IBDs) are chronic inﬂammatory disorders of the GI tract consisting primarily of two subtypes, ulcerative colitis (UC) and Crohn’s disease (CD). CD is characterized by transmural inﬂammation of any portion of the GI tract from mouth to anus, whereas UC is limited to the colon and rectum with inﬂammation typically restricted to the mucosa, although inﬂammatory involvement of the submucosa may occur in severe cases. Both CD and UC are characterized by an inﬂux of inﬂammatory cells, especially leukocytes into gut mucosal tissue. An important leukocyte involved in the pathogenesis of both CD and UC is the α4β7-integrin-expressing T cell. Integrins, which consist of an α- and β-chain that together form a heterodimer, bind to ligands on endothelial cells, allowing leukocytes to firmly adhere to endothelial surfaces.
Extravasation of leukocytes from the blood into stromal tissues of gut mucosal tissue is a complex process involving a coordinated sequence of events between leukocytes and vascular endothelial cells. Several steps – tethering/rolling, activation, adhesion and extravasation/migration occur allowing immune cells to enter stromal tissues. Initially, leukocytes tether to the vascular endothelium through multiple transient interactions between selectins on leukocytes such as PSGL-1 and their ligands on the endothelial surface (P-selectin and E-selectin). This process decreases the speed of leukocytes to facilitate rolling along the endothelial surface. The slower speed of these leukocytes permits interactions to occur between integrins on the surface of the leukocyte and their ligands on the endothelium. Slowing leukocytes also allows chemokines from inflamed tissue to activate them resulting in leukocyte polarization, while also enhancing the binding affinity of integrins. When activated, these cells preferentially adhere to endothelial surfaces within the GI tract as well as the associated lymphoid tissues. Upon activation, α4β7-integrin-expressing T cells bind to their ligand MAdCAM-1 and leukocytes are primed for extravasation. Leukocytes subsequently cross the endothelium and enter the mucosa through a paracellular route.
Abrilumab, sharing the same mechanism of Action with another monoclonal antibody—Vedolizumab, was also designed specifcally targets α4β7, so that preventing the α4β7/MAdCAM-1 interaction, hence inhibiting leukocyte migration into gut mucosa.