{"id":6485,"date":"2020-08-24T18:08:36","date_gmt":"2020-08-24T18:08:36","guid":{"rendered":"https:\/\/cdtrp.ca\/?p=6485"},"modified":"2020-08-24T18:08:36","modified_gmt":"2020-08-24T18:08:36","slug":"article-en-vedette-functional-effects-of-chimeric-antigen-receptor-co-receptor-signaling-domains-in-human-regulatory-t-cells","status":"publish","type":"post","link":"https:\/\/cdtrp.ca\/fr\/article-en-vedette-functional-effects-of-chimeric-antigen-receptor-co-receptor-signaling-domains-in-human-regulatory-t-cells\/","title":{"rendered":"Article en vedette : Functional effects of chimeric antigen receptor co-receptor signaling domains in human regulatory T cells"},"content":{"rendered":"<div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-1 nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-0 fusion_builder_column_1_1 1_1 fusion-one-full fusion-column-first fusion-column-last\" style=\"--awb-bg-size:cover;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-column-wrapper-legacy\"><div class=\"fusion-text fusion-text-1\"><h4>Article en vedette : <em>Functional effects of chimeric antigen receptor co-receptor signaling domains in human regulatory T cells<\/em><\/h4>\n<p style=\"text-align: left;\"><span style=\"font-size: 16px; font-weight: 400;\">Le PRDTC tient \u00e0 f\u00e9liciter Megan Levings et tous ses collaborateurs qui ont travaill\u00e9 sur l&rsquo;article \u00ab\u00a0<em><strong>Functional effects of chimeric antigen receptor co-receptor signaling domains in human regulatory T cells<\/strong><\/em>\u00ab\u00a0, r\u00e9cemment publi\u00e9 dans <em>Science &#8211; Translational Medicine<\/em>!<\/span><\/p>\n<h5 style=\"text-align: left;\">R\u00e9sum\u00e9 (en anglais)<\/h5>\n<p style=\"text-align: left;\">Antigen-specific regulatory T cells (Tregs) engineered with chimeric antigen receptors (CARs) are a potent immunosuppressive cellular therapy in multiple disease models and could overcome shortcomings of polyclonal Treg therapy. CAR therapy was initially developed with conventional T cells, which have different signaling requirements than do Tregs. To date, most of the CAR Treg studies used second-generation CARs, encoding a CD28 or 4-1BB co-receptor signaling domain and CD3\u03b6, but it was not known if this CAR design was optimal for Tregs. Using a human leukocyte antigen\u2013A2\u2013specific CAR platform and human Tregs, we compared 10 CARs with different co-receptor signaling domains and systematically tested their function and CAR-stimulated gene expression profile. Tregs expressing a CAR encoding CD28wt were markedly superior to all other CARs tested in an in vivo model of graft-versus-host disease. In vitro assays revealed stable expression of Helios and an ability to suppress CD80 expression on dendritic cells as key in vitro predictors of in vivo function. This comprehensive study of CAR signaling domain variants in Tregs can be leveraged to optimize CAR design for use in antigen-specific Treg therapy.<\/p>\n<h5><a href=\"https:\/\/stm.sciencemag.org\/content\/12\/557\/eaaz3866\">Vous pouvez lire l&rsquo;article ici<\/a> (en anglais).<\/h5>\n<\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"margin-left: auto;margin-right: auto;margin-top:30px;margin-bottom:30px;width:100%;\"><div class=\"fusion-separator-border sep-single sep-solid\" style=\"--awb-height:20px;--awb-amount:20px;border-color:#e0dede;border-top-width:2px;\"><\/div><\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-image-element fusion-image-align-center in-legacy-container\" style=\"text-align:center;--awb-caption-title-font-family:var(--h2_typography-font-family);--awb-caption-title-font-weight:var(--h2_typography-font-weight);--awb-caption-title-font-style:var(--h2_typography-font-style);--awb-caption-title-size:var(--h2_typography-font-size);--awb-caption-title-transform:var(--h2_typography-text-transform);--awb-caption-title-line-height:var(--h2_typography-line-height);--awb-caption-title-letter-spacing:var(--h2_typography-letter-spacing);\"><div class=\"imageframe-align-center\"><span class=\" fusion-imageframe imageframe-dropshadow imageframe-1 hover-type-none\" style=\"-webkit-box-shadow: 3px 3px 7px rgba(0,0,0,0.3);box-shadow: 3px 3px 7px rgba(0,0,0,0.3);\"><img decoding=\"async\" width=\"592\" height=\"412\" title=\"Levings, Megan 3\" src=\"https:\/\/cdtrp.ca\/wp-content\/uploads\/2020\/08\/Levings-Megan-3.png\" data-orig-src=\"https:\/\/cdtrp.ca\/wp-content\/uploads\/2020\/08\/Levings-Megan-3.png\" alt class=\"lazyload img-responsive wp-image-6491\" srcset=\"data:image\/svg+xml,%3Csvg%20xmlns%3D%27http%3A%2F%2Fwww.w3.org%2F2000%2Fsvg%27%20width%3D%27592%27%20height%3D%27412%27%20viewBox%3D%270%200%20592%20412%27%3E%3Crect%20width%3D%27592%27%20height%3D%27412%27%20fill-opacity%3D%220%22%2F%3E%3C%2Fsvg%3E\" data-srcset=\"https:\/\/cdtrp.ca\/wp-content\/uploads\/2020\/08\/Levings-Megan-3-200x139.png 200w, https:\/\/cdtrp.ca\/wp-content\/uploads\/2020\/08\/Levings-Megan-3-400x278.png 400w, https:\/\/cdtrp.ca\/wp-content\/uploads\/2020\/08\/Levings-Megan-3.png 592w\" data-sizes=\"auto\" data-orig-sizes=\"(max-width: 1024px) 100vw, 592px\" \/><\/span><\/div><\/div><div class=\"fusion-clearfix\"><\/div><\/div><\/div><\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":6,"featured_media":6489,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[81,37],"tags":[],"class_list":["post-6485","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-en-vedette","category-non-classifiee"],"_links":{"self":[{"href":"https:\/\/cdtrp.ca\/fr\/wp-json\/wp\/v2\/posts\/6485"}],"collection":[{"href":"https:\/\/cdtrp.ca\/fr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cdtrp.ca\/fr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cdtrp.ca\/fr\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/cdtrp.ca\/fr\/wp-json\/wp\/v2\/comments?post=6485"}],"version-history":[{"count":3,"href":"https:\/\/cdtrp.ca\/fr\/wp-json\/wp\/v2\/posts\/6485\/revisions"}],"predecessor-version":[{"id":6534,"href":"https:\/\/cdtrp.ca\/fr\/wp-json\/wp\/v2\/posts\/6485\/revisions\/6534"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cdtrp.ca\/fr\/wp-json\/wp\/v2\/media\/6489"}],"wp:attachment":[{"href":"https:\/\/cdtrp.ca\/fr\/wp-json\/wp\/v2\/media?parent=6485"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cdtrp.ca\/fr\/wp-json\/wp\/v2\/categories?post=6485"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cdtrp.ca\/fr\/wp-json\/wp\/v2\/tags?post=6485"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}