{"id":277,"date":"2018-03-07T16:06:51","date_gmt":"2018-03-07T15:06:51","guid":{"rendered":"http:\/\/projects.nib.si\/itfcart\/?page_id=277"},"modified":"2022-04-05T18:48:34","modified_gmt":"2022-04-05T17:48:34","slug":"project-phases-and-realisation","status":"publish","type":"page","link":"https:\/\/projects.nib.si\/iTFCarT\/project-phases-and-realisation\/","title":{"rendered":"Project phases and realisation"},"content":{"rendered":"<p>Our research project aims to fill the gaps described in the \u201c<a title=\"Permalink to Short description\" href=\"http:\/\/projects.nib.si\/iTFCarT\/\" rel=\"bookmark\">Short description<\/a>\u201d section to improve CAR T cells targeting CD19-positive hematological malignancies. We will achieve this by:<\/p>\n<p>(<strong>i<\/strong>) Incorporating the key transcription factors (TFs) identified in our previous studies as important candidates for improving the intrinsic T cell properties; and<\/p>\n<p>(<strong>ii<\/strong>) Genetic integration of these candidate molecules into CAR T cells to enable constitutive or inducible expression (<strong>TF-CAR T cells<\/strong>).<\/p>\n<p>In <strong>Objective 1<\/strong>, we will utilize a novel genetic platform called <strong>Uni-Vect<\/strong>, developed by the PI of this project, while he was working at the University of Pennsylvania (UPenn). Uni-Vect will allow for transient expression of TFs in CAR T cells. Additionally, we will design and test systems with constitutively expressed TFs (cTF-CAR T cells). We will create CD19-targeting CAR T cells upgraded with ectopic expression of two key transcription factors with a hypothesis to create CAR T cells with a fitness profile associated with a capacity to expand, persist and mediate cancer regression after infusion.<\/p>\n<p>In <strong>Objective 2<\/strong>, we will establish <em>in vitro<\/em> systems that will enable us to evaluate and compare functional and phenotypic properties of i\/cTF-CAR T cells. Using advanced immunological approaches, we will examine the mechanisms that lead to the potential improved functions. In collaboration with our partners from the US, we will also investigate whether i\/cTF-CAR T cells can improve activity against chronic lymphocytic leukemia (CLL) and improve T cell manufacturing in difficult-to-expand T cells.<\/p>\n<p>In <strong>Objective 3<\/strong>, we will test i\/cTF-CAR T cell products in xenograft and syngeneic preclinical mouse models and determine the impact of ectopic expression of TFs on CAR T cell expansion, persistence and anti-tumor activity <em>in vivo<\/em>. We will isolate CAR T cells from mice and examine CAR T cell phenotype and function to gain a better understanding of which key factors contribute to improved T-cell intrinsic properties. This will inform further developments of i\/cTF-CAR T cell approaches.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Our research project aims to fill the gaps described in the \u201cShort description\u201d section to improve CAR T cells targeting CD19-positive hematological malignancies. We will achieve this by: (i) Incorporating the key transcription factors (TFs) identified in our previous studies as important candidates for improving the intrinsic T cell properties; and (ii) Genetic integration of [&hellip;]<\/p>\n","protected":false},"author":4,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-277","page","type-page","status-publish","hentry"],"jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/P7OqMV-4t","jetpack-related-posts":[],"_links":{"self":[{"href":"https:\/\/projects.nib.si\/iTFCarT\/wp-json\/wp\/v2\/pages\/277","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/projects.nib.si\/iTFCarT\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/projects.nib.si\/iTFCarT\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/projects.nib.si\/iTFCarT\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/projects.nib.si\/iTFCarT\/wp-json\/wp\/v2\/comments?post=277"}],"version-history":[{"count":12,"href":"https:\/\/projects.nib.si\/iTFCarT\/wp-json\/wp\/v2\/pages\/277\/revisions"}],"predecessor-version":[{"id":345,"href":"https:\/\/projects.nib.si\/iTFCarT\/wp-json\/wp\/v2\/pages\/277\/revisions\/345"}],"wp:attachment":[{"href":"https:\/\/projects.nib.si\/iTFCarT\/wp-json\/wp\/v2\/media?parent=277"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}