{"id":32152,"date":"2024-08-15T13:53:41","date_gmt":"2024-08-15T17:53:41","guid":{"rendered":"https:\/\/www.cancerresearch.org\/?post_type=cri_scientists&#038;p=32152"},"modified":"2024-08-15T13:53:41","modified_gmt":"2024-08-15T17:53:41","slug":"jennifer-l-clarke-md","status":"publish","type":"cri_scientists","link":"https:\/\/www.cancerresearch.org\/es\/cri-funded-scientists\/jennifer-l-clarke-md","title":{"rendered":"Jennifer L. Clarke, MD"},"content":{"rendered":"\n<p>To safely and effectively target glioblastoma (GBM)-associated antigens (GAAs), Dr. Clarke has adopted a novel synthetic Notch &#8216;synNotch&#8217; receptor system. In this system, the first antigen, which is expressed exclusively on GBM cells (e.g., EGFRvIII), primes the T cells to induce expression of a CAR that recognizes IL-13R\u03b12 and EphA2, thereby eradicating GBM cells expressing either EphA2 or IL-13R\u03b12. Dr. Clarke has demonstrated that EGFRvIII-synNotch primed EphA2\/IL-13R\u03b12 CAR (E-SYNC) are effectively but restrictedly activated by EGFRvIII as the GBM-specific signal, thereby leading to complete eradication of orthotopic patient-derived xenografts (PDX) with heterogeneous EGFRvIII expression, without attacking EphA2\/IL-13R\u03b12-positive cells outside of the CNS. Furthermore, these synNotch-CART cells were significantly more efficacious than conventional EphA2\/IL-13R\u03b12 CART cells, associated with excellent persistence, and more juvenile in phenotype than conventional CART cells5. \u00a0\u00a0<\/p>\n\n\n\n<p>In this study, Dr. Clarke will conduct a first-in-human phase I study to evaluate the hypothesis that a single IV infusion of E-SYNC T cells in patients with EGFRvIII+ GBM will be safe and that the IV-infused E-SYNC T cells will demonstrate local priming in prospectively resected GBM tissue. The study has been developed with the following sequential two cohorts to evaluate:&nbsp;<\/p>\n\n\n\n<p>1. The safety of IV-infused E-SYNC T cells in patients with newly diagnosed GBM (Cohort 1) as a dose-escalation cohort.\u00a0<\/p>\n\n\n\n<p>2. The infiltration and priming of the pre-surgically IV-infused E-SYNC T cells in the resected tumor tissue (Cohort 2).<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Projects and Grants<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\"><strong>Phase 1 study of autologous anti-EGFRvIII synNotch receptor-induced anti-EphA2\/IL-13R\u03b12 CAR (E-SYNC) T Cells in adult participants with EGFRvIII+ glioblastoma<\/strong><\/h3>\n\n\n\n<p>University of California, San Francisco | Brain Cancer | 2024<\/p>\n","protected":false},"excerpt":{"rendered":"<p>To safely and effectively target glioblastoma (GBM)-associated antigens (GAAs), Dr. Clarke has adopted a novel synthetic Notch &#8216;synNotch&#8217; receptor system. In this system, the first antigen, which is expressed exclusively on GBM [&hellip;]<\/p>\n","protected":false},"featured_media":32207,"template":"","tax_cancer_type":[366],"tax_grant_type":[725],"tax_award_year":[741],"tax_institutions":[500],"tax_location_states":[501],"class_list":["post-32152","cri_scientists","type-cri_scientists","status-publish","has-post-thumbnail","hentry"],"acf":{"scientist_subhead":"Clinical Accelerator Investigator","quote":"We are conducting a first-in-human phase 1 clinical trial testing E-SYNC CAR T cells, a home-grown CAR T cell product developed entirely at UCSF and applied to the challenging disease of glioblastoma.","scientist_last_name":"Clarke","show_on_landing":true,"scientist_publish_until":"20280831"},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Jennifer L. 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