{"id":7996,"date":"2020-11-16T21:40:35","date_gmt":"2020-11-16T21:40:35","guid":{"rendered":"https:\/\/cdtrp.ca\/?p=7996"},"modified":"2020-11-16T21:40:35","modified_gmt":"2020-11-16T21:40:35","slug":"ast-ajt-journal-club-november-24-dr-megan-levings","status":"publish","type":"post","link":"https:\/\/cdtrp.ca\/en\/ast-ajt-journal-club-november-24-dr-megan-levings\/","title":{"rendered":"AST\/AJT Journal Club &#8211; November 24: Dr. Megan Levings"},"content":{"rendered":"<div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-1 fusion-flex-container 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 fusion-flex-align-items-flex-start fusion-flex-content-wrap\" style=\"max-width:1216.8px;margin-left: calc(-4% \/ 2 );margin-right: calc(-4% \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-0 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:0px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-text fusion-text-1\"><h3>AST\/AJT Journal Club November 24: Dr. Megan Levings<\/h3>\n<p>The <a href=\"https:\/\/www.myast.org\/\">American Society of Transplantation<\/a> (AST) and the <a href=\"https:\/\/onlinelibrary.wiley.com\/journal\/16006143\">American Journal of Transplantation<\/a> (AJT) invite the transplant community to join the Journal Club based on this article published in <em>Science Translational Medicine<\/em> in August 2020: <a href=\"https:\/\/stm.sciencemag.org\/content\/12\/557\/eaaz3866\" target=\"_blank\" rel=\"noopener noreferrer\">&#8220;Functional effects of chimeric antigen receptor co-receptor signaling domains in human regulatory T cells.&#8221;<\/a><\/p>\n<h5 style=\"text-align: center;\" data-pm-slice=\"1 1 &#091;&#093;\"><strong>November 24, 2020 at 2:00pm EST &#8211; <a href=\"https:\/\/register.gotowebinar.com\/register\/7068163630296060944\">Register here.<\/a><\/strong><\/h5>\n<h5 data-pm-slice=\"1 1 &#091;&#093;\">Speaker:<\/h5>\n<ul>\n<li>Megan Levings, PhD \u2022 University of British Columbia, Vancouver, BC<\/li>\n<\/ul>\n<h5>Moderator:<\/h5>\n<ul>\n<li>Olivia Martinez, PhD \u2022 Stanford University, Stanford, CA<\/li>\n<\/ul>\n<h5>Q&amp;A Guests:<\/h5>\n<ul>\n<li>Nicholas Dawson, PhD \u2022 University of British Columbia, Vancouver, BC<\/li>\n<li>Isaac Rosado-S\u00e1nchez, PhD \u2022 BC Children&#8217;s Hospital Research Institute, Vancouver, BC<\/li>\n<\/ul>\n<p><i>Journal clubs are free for both members and non-members. Pre-registration is required.<\/i><\/p>\n<\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"align-self: center;margin-left: auto;margin-right: auto;margin-top:20px;margin-bottom:20px;width:100%;\"><\/div><div class=\"fusion-text fusion-text-2\"><h4>Abstract<\/h4>\n<p>Antigen-specific regulatory T cells (T<sub>regs<\/sub>) engineered with chimeric antigen receptors (CARs) are a potent immunosuppressive cellular therapy in multiple disease models and could overcome shortcomings of polyclonal T<sub>reg<\/sub>\u00a0therapy. CAR therapy was initially developed with conventional T cells, which have different signaling requirements than do T<sub>regs<\/sub>. To date, most of the CAR T<sub>reg<\/sub>\u00a0studies 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 T<sub>regs<\/sub>. Using a human leukocyte antigen\u2013A2\u2013specific CAR platform and human T<sub>regs<\/sub>, we compared 10 CARs with different co-receptor signaling domains and systematically tested their function and CAR-stimulated gene expression profile. T<sub>regs<\/sub>\u00a0expressing 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 T<sub>regs<\/sub>\u00a0can be leveraged to optimize CAR design for use in antigen-specific T<sub>reg<\/sub>\u00a0therapy.<\/p>\n<h4 style=\"text-align: center;\"><a href=\"https:\/\/register.gotowebinar.com\/register\/7068163630296060944\">Click here to register for free.<\/a><\/h4>\n<\/div><\/div><\/div><\/div><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":6,"featured_media":7998,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1,75],"tags":[],"class_list":["post-7996","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-general","category-featured"],"_links":{"self":[{"href":"https:\/\/cdtrp.ca\/en\/wp-json\/wp\/v2\/posts\/7996"}],"collection":[{"href":"https:\/\/cdtrp.ca\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cdtrp.ca\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cdtrp.ca\/en\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/cdtrp.ca\/en\/wp-json\/wp\/v2\/comments?post=7996"}],"version-history":[{"count":2,"href":"https:\/\/cdtrp.ca\/en\/wp-json\/wp\/v2\/posts\/7996\/revisions"}],"predecessor-version":[{"id":8117,"href":"https:\/\/cdtrp.ca\/en\/wp-json\/wp\/v2\/posts\/7996\/revisions\/8117"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cdtrp.ca\/en\/wp-json\/wp\/v2\/media\/7998"}],"wp:attachment":[{"href":"https:\/\/cdtrp.ca\/en\/wp-json\/wp\/v2\/media?parent=7996"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cdtrp.ca\/en\/wp-json\/wp\/v2\/categories?post=7996"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cdtrp.ca\/en\/wp-json\/wp\/v2\/tags?post=7996"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}