{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:40:10Z","timestamp":1787010010539,"version":"build-2736575974"},"reference-count":76,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Chimeric antigen receptor (CAR)\u2010T cell therapy is a new class of cellular immunotherapies that involves ex vivo genetic modification of T cells to incorporate an engineered CAR. After infusion into the patient, the CAR\u2010expressing T cells recognize specific tumor targets and induce an immune response against them. The technology utilized is fundamentally different from previously available cancer treatments. Currently, most CAR\u2010T cell therapies use autologous T cells. Tisagenlecleucel (formerly CTL019) is an anti\u2010CD19 CAR\u2010T cell therapy that was recently approved in the United States for the treatment of pediatric and young adult patients with relapsed\/refractory B\u2010cell acute lymphoblastic leukemia (B\u2010ALL). Tisagenlecleucel has shown robust in vivo expansion and long\u2010term persistence, clinically meaningful durable response and remission rates, and overall survival benefit in pediatric and young adult patients with relapsed\/refractory B\u2010ALL and in relapsed\/refractory diffuse large B\u2010cell lymphoma. Common adverse events (AEs) include cytokine release syndrome, which may require hospitalization and admission to an intensive care unit, neurological toxicities, and B\u2010cell aplasia. These AEs are manageable when treated by an appropriately trained team. Additional research is required to further develop AE management protocols. In this review, we describe regulatory requirements, clinical considerations, and site\u2010level requirements for clinical study implementation of CAR\u2010T cell therapy in Europe. We also provide a case study of the European experience from the first global clinical trial for tisagenlecleucel, which may serve as a useful starting point for investigators and clinicians looking to implement CAR\u2010T cell therapy at their institutions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/hs9.0000000000000018","type":"journal-article","created":{"date-parts":[[2018,2,4]],"date-time":"2018-02-04T18:52:51Z","timestamp":1517770371000},"source":"Crossref","is-referenced-by-count":38,"title":["Chimeric Antigen Receptor\u2010T Cell Therapy"],"prefix":"10.1002","volume":"2","author":[{"given":"Jochen","family":"Buechner","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Jos\u00e9","family":"Kersten","sequence":"additional","affiliation":[{"name":"Department of Hematology Academic Medical Center University of Amsterdam 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Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2016.12.006"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/mto.2016.15"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac5415"},{"issue":"1","key":"e_1_2_14_5_1","first-page":"183","article-title":"Durable remissions after monotherapy with CD19\u2010specific chimeric antigen receptor (CAR)\u2010modified T cells in children and young adults with relapsed\/refractory ALL [Abstract S497]","volume":"101","author":"Maude S","year":"2016","journal-title":"Haematologica"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V128.22.2801.2801"},{"issue":"2","key":"e_1_2_14_7_1","first-page":"178","article-title":"Global registration trial of efficacy and safety of CTL019\u00a0in pediatric and young adult 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