Common-Gamma Receptor Antagonists

Cytokines are mediators of the immune system and drive vital functions such as cellular growth, differentiation, and prevention or promotion of programmed cell death. A group of very important cytokines that share a common receptor named gamma-c (γc) or CD132 is called γc-cytokines[1]. They include 6 known cytokines (IL-2, -4, -7, -9, 15, and -21, which are collectively called γc-family cytokines)[2]. These cytokines play a crucial role in the early development of T cells in the thymus as well as their homeostasis in the periphery. Mice lacking this receptor do not develop B-, T-, and NK-cells and are severely immuno-compromised[3]. A mutation in this receptor in human will rise into X-linked severe combined immunodeficiency[4]. This clearly indicates the critical role of this receptor and its cytokines in the immune system and identifies it as a valid therapeutic target. However, thus far an effectively blocking monoclonal antibody against γc has not been available. As an alternative strategy, a class of small molecules called JAK3 inhibitors was developed to interrupt the downstream signaling pathway to this receptor[5]. The problem with JAK3 inhibitors are their lack of specificity towards other cellular components which causes severe side effects such as anemia and repeated infection[6].</p> <p>Bioniz has designed first-in-class antagonist peptides that target the γc receptor and inhibit the binding of this receptor to its ligands. Furthermore, the γc antagonistic peptides can “selectively inhibit” some of the γc –cytokines but not the rest. This class of antagonist peptides against the γc receptor is called BNZ-gamma (BNZ-γ).</p> <CENTER><img src="/images/common_gamma_receptor_antagonists.jpg" alt="" /></CENTER> <p></p> <p>The selective inhibition property of Bioniz technology is advantageous as it will give the γc targeted therapy the flexibility of blocking only the cytokines that are culprit in any immune-mediated disease. This supremely focused targeted therapy limits the potential side effects associated with immune-modulation. For example, an antagonist peptide blocking only IL-21 and IL-15 will be a candidate in treating celiac disease[7]. Or a peptide that inhibits IL-2, and IL-15 will be advantageous in T-cell mediated diseases[8]. Similarly, a peptide that disrupts the function of IL-4 will have application in asthma and other allergic diseases[9].</p> <p></p> <b>References:</b> <p>1- Takeshita, T., Asao, H., Ohtani, K., Ishii, N., Kumaki, S., Tanaka, N., Manukata, H., Nakamura, M., Sugamura, K., Cloning of the Gamma chain of the Human IL2 receptor. 1992 Science 257:379-382.</p> <p>2- Sugamura, K., Asao, H., Kondo, M., Tanaka, N., Ishii, N., Nakamura, M., Takeshita, T., The common gamma-chain for multiple cytokine receptors. 1995 Adv. Immunol. 59: 225-277.</p> <p>3- Sugamura, K., Asao, H., Kondo, M., Tanaka, N., Ishii, N., Ohbo, K., Nakamura, M., Takeshita, T., The interleukin-2 receptor gamma chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. 1996 Annu. Rev. Immunol. 14:179-205.</p> <p>4- Noguchi, M., Yi, H., Rosenblatt, H.M., Filipovich, A.H., Adelstein, S., Modi, W.S., McBride, O.W., Leonard, W.J., Interleukin 2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. 1993 Cell 73:147-157.</p> <p>5- Pesu M, Candotti F, Husa M, Hofmann SR, Notarangelo LD, and O’Shea JJ. Jak3, severe combined immunodeficiency, and a new class of immunosuppressive drugs. 2005 Immunol. Rev. 203:127-142.</p> <p>6- O’Shea, J.J., Targeting the Jak/STAT pathway for immunosuppression. 2004 Ann. Rheum. Dis. 63:(suppl II): ii67-71.</p> <p>7- Bodd, M., Raki, M., Tollefsen, S., Fallang, L.E., Bergseng, E., Lundin, K.E., Sollid, L.M., HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22. 2010 Mucosal Immunol. 3:594-601.</p> <p>8- Sarra M, et al. IL-21 promotes skin recruitment of CD4(+) cells and drives IFN-γ-dependent epidermal hyperplasia. 2011 J Immunol. 186:5435-42.</p> <p>9- Le Buanec, H., Paturance, S., Couillin, I., Schnyder-Candrian, S., Larcier, P., Ryffel, B., Bizzini, B., Bensussan, A., Burny, A., Gallo, R., Zagury, D., Peltre, G., Control of allergic reactions in mice by an active anti-murine IL-4 immunization. 2007 Vaccine 25:7206-16.</p> </div> </div> </div> <div class="clear"></div><br /> <div class="clear"></div> </div> </div> <div class="base-content"></div> </div>   <div class="footer-wrap"> <div class="footer"> <div class="left"> <ul> <li><a href="http://www.bioniz.com/about_us/index.php" title="About Us">About Us</a></li> <li class="separator">|</li> <li><a href="http://www.bioniz.com/technology/index.php" title="Technology">Technology</a></li> <li class="separator">|</li> <li><a href="http://www.bioniz.com/pipeline_diseasefocus/index.php" title="Pipeline & Disease Focus">Pipeline & Disease Focus</a></li> <li class="separator">|</li> <li><a href="http://www.bioniz.com/investors_newsroom/index.php" title="Investors & News Room">Investors & News Room</a></li> <li class="separator"></li>  <li class="separator">|</li> <li><a href="http://www.bioniz.com/contact_us.php" title="Contact Us">Contact Us</a></li> </ul> <ul> <li><a href="http://www.bioniz.com/sitemap.php" title="Site Map">Site Map</a></li> <li class="separator">|</li> <li><a href="http://www.bioniz.com/terms.php" title="Contact Us">Terms of Use</a></li> <li class="separator">|</li> <li><a href="http://www.bioniz.com/privacy.php" title="Privacy Policy">Privacy Policy</a></li> </li> </ul> </div> <div class="right"> <ul> <li>© 2012 <a href="http://www.bioniz.com/index.php" title="Home">BIONIZ</a></li> </ul> </div> <div class="clear"></div> </div> </div>  <script type="text/javascript"> var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); </script> <script type="text/javascript"> var pageTracker = _gat._getTracker("UA-18351715-3"); pageTracker._trackPageview(); </script> </body> </html>

BIONIZBIONIZ

Common-Gamma Receptor Antagonists

Common-Gamma Receptor Antagonists