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<h4><br>To solve the problems existing in the current treatment of RA, we design and build a brand new immunotherapy. FOXP3+ regulatory T cells, which can suppress and regulate immune reaction, are engineered by inserting a chimeric antigen receptor (CAR) using lentiviral vectors to recognize RA related inflammatory cells. At the same time, we insert another receptor to activate the functional stability pathway of regulatory T cells in the inflammatory environment, thus making it possible for them to be more immunosuppressive and more stable in lesions in hope for a better anti-RA effect. These two redirections of the two different systems on the native regulatory T cell response ensure both the efficacy and efficiency of our novel immunotherapy for RA.</h4> | <h4><br>To solve the problems existing in the current treatment of RA, we design and build a brand new immunotherapy. FOXP3+ regulatory T cells, which can suppress and regulate immune reaction, are engineered by inserting a chimeric antigen receptor (CAR) using lentiviral vectors to recognize RA related inflammatory cells. At the same time, we insert another receptor to activate the functional stability pathway of regulatory T cells in the inflammatory environment, thus making it possible for them to be more immunosuppressive and more stable in lesions in hope for a better anti-RA effect. These two redirections of the two different systems on the native regulatory T cell response ensure both the efficacy and efficiency of our novel immunotherapy for RA.</h4> | ||
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− | <img src="./ | + | <center><img src="https://static.igem.org/mediawiki/2017/5/56/T--CPU_CHINA--des-figure4.png"width = "700"></center> |
− | < | + | <center>Figure 1</center> |
</div> | </div> | ||
<h3 class="ar-title">SynNotch System</h3> | <h3 class="ar-title">SynNotch System</h3> | ||
<h4><br>SynNotch is a system that is capable of specifically activating the expression of the USP7 gene in an inflammatory environment, thereby maintaining the activity of Treg cells by stabilizing the FOXP3 proteins.</h4> | <h4><br>SynNotch is a system that is capable of specifically activating the expression of the USP7 gene in an inflammatory environment, thereby maintaining the activity of Treg cells by stabilizing the FOXP3 proteins.</h4> | ||
− | <div | + | <div> |
− | <img src="./ | + | <center><img src="https://static.igem.org/mediawiki/2017/5/53/T--CPU_CHINA--eng-figure3_7.png" width = "700"></center> |
− | < | + | <center>Figure 2</center> |
</div> | </div> | ||
<h4><br>In our SynNotch system, we retain the functional sequence of the transmembrane domain and the cleavage site of the Notch 1 protein. At the N-terminus, we fuse the extracellular domain of IL17RA with Notch 1 to specifically recognize IL-17A secreted by Th17 cells, so that our regulatory T cells to obtain the ability to response to IL-17A. We also connect the gene of Gal4-vp64 (a fusion protein) in the downstream of Notch 1. In the presence of inflammatory cytokines IL17A, SynNotch protein is cleaved, and thus Gal4-VP64 fusion protein is detached from the cell membrane. </h4> | <h4><br>In our SynNotch system, we retain the functional sequence of the transmembrane domain and the cleavage site of the Notch 1 protein. At the N-terminus, we fuse the extracellular domain of IL17RA with Notch 1 to specifically recognize IL-17A secreted by Th17 cells, so that our regulatory T cells to obtain the ability to response to IL-17A. We also connect the gene of Gal4-vp64 (a fusion protein) in the downstream of Notch 1. In the presence of inflammatory cytokines IL17A, SynNotch protein is cleaved, and thus Gal4-VP64 fusion protein is detached from the cell membrane. </h4> | ||
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<h3 class="ar-title">CAR System</h3> | <h3 class="ar-title">CAR System</h3> | ||
<h4><br>CAR-CD20 is a module that enables engineered modified T cells to specifically recognize the surface antigen CD20 in B lymphocytes and thus to play anti-inflammatory function. Our CAR-CD20 system is made up of the gene sequences of several proteins. </h4> | <h4><br>CAR-CD20 is a module that enables engineered modified T cells to specifically recognize the surface antigen CD20 in B lymphocytes and thus to play anti-inflammatory function. Our CAR-CD20 system is made up of the gene sequences of several proteins. </h4> | ||
− | <div | + | <div> |
− | <img src="./ | + | <center><img src="https://static.igem.org/mediawiki/2017/5/5a/T--CPU_CHINA--eng-figure3_9.png" width = "700"></center> |
− | < | + | <center>Figure 3</center> |
</div> | </div> | ||
<h4><br>At the N terminus, we choose variable region of CD20 monoclonal antibody as the scFv fragment, so that it can accurately identify and bind to B lymphocyte surface antigen CD20. Then, we use two 4-1-BB sequences as a co-stimulatory signal and a CD3Z sequence as a stimulatory signal that allow the signal to be delivered to the cell at a high level, thereby activating Treg cells in the presence of CD20 B lymphocytes. </h4> | <h4><br>At the N terminus, we choose variable region of CD20 monoclonal antibody as the scFv fragment, so that it can accurately identify and bind to B lymphocyte surface antigen CD20. Then, we use two 4-1-BB sequences as a co-stimulatory signal and a CD3Z sequence as a stimulatory signal that allow the signal to be delivered to the cell at a high level, thereby activating Treg cells in the presence of CD20 B lymphocytes. </h4> |
Revision as of 13:49, 30 October 2017