Talk:Etrolizumab

Etrolizumab Recommended Content Correction
My name is Austine Graff from Genentech, Inc. We are developing Etrolizumab. We noticed information about Etrolizumab is inaccurate and I wanted to make sure I addressed it in the appropriate manner.

We believe the following text within the Monoclonal Antibody box on the right hand side of the Etrolizumab page to be inaccurate: “Target integrin a7β7”

PROPOSED REVISION

My team at Genentech would invite you to consider the following new text: “Target β7 subunit of the α4β7 and αEβ7 integrins” Here are URL links to sources for this suggestion and the excerpts from each source that specifically address this topic:
 * Source 1: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2960661-9/fulltext
 * “Etrolizumab, a humanised monoclonal antibody that selectively binds the β7 subunit of both the α4β7 and αEβ7 integrin heterodimers, antagonises α4β7-MAdCAM-1-mediated egress of lymphocytes from the mucosal vasculature and αEβ7-E-cadherin interactions that are believed to be involved in retention of αEβ7 cells in the intraepithelial compartment.”
 * Source 2: http://gut.bmj.com/content/62/8/1122.long
 * “Migration into the gastrointestinal tract is highly dependent on interactions between the α4β7 integrin expressed on the surface of the leucocyte and its ligand, mucosal addressin cell adhesion molecule (MAdCAM-1) expressed on endothelial cells. α4β7 Binds preferentially to MAdCAM-1 expressed on the high endothelial venules of mucosal-associated lymphoid tissues, and has limited binding to vascular cell adhesion molecule 1 (VCAM-1) and the fibronectin fragment CS-1. α4β7+ Cells and MAdCAM-1 expression are elevated at sites of chronic inflammation such as in the intestinal tract of patients with UC. The αEβ7 integrin, another member of the β7 integrin family, is expressed exclusively on mucosal intraepithelial T lymphocytes.”
 * Source 3: http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01205.x/full
 * “In cynomolgus monkeys, occupancy of β7 integrin receptors by rhuMAb Beta7 correlated with an increase in circulating β7+ mucosal-homing lymphocytes, with no apparent effect on levels of circulating β7- peripheral-homing lymphocytes. rhuMAb Beta7 also inhibited lymphocyte homing to the inflamed colons of severe combined immunodeficient mice in CD45RBhigh CD4+ T-cell transfer models. Consistent with a lack of effect on peripheral homing, in a mouse model of experimental autoimmune encephalomyelitis, anti-β7 treatment resulted in no amelioration of CNS inflammation.”

My team would also invite you to consider adding the following clinicaltrials.gov link to the “References” section of the Etrolizumab page: http://clinicaltrials.gov/ct2/results?term=etrolizumab&Search=Search”

Please let me know if there are any questions. I’ll continue to watch this space to see if the updates have been approved and implemented.

<--End request--> Graffa2 (talk) 22:30, 30 October 2014 (UTC)