Research Article| Volume 19, ISSUE 6, P703-709, June 2017

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Understanding clinical development of chimeric antigen receptor T cell therapies

Published:April 19, 2017DOI:


      Background aims

      In the past decade, many clinical trials with gene- and cell-based therapies (GCTs) have been performed. Increased interest in the development of these drug products by various stakeholders has become apparent. Despite this growth in clinical studies, the number of therapies receiving marketing authorization approval (MAA) is lagging behind. To enhance the success rate of GCT development, it is essential to better understand the clinical development of these products. Chimeric antigen receptor (CAR) T cells are a GCT product subtype with promising efficacy in cancer treatment which are tested in many clinical trials, but have not yet received MAA.


      We generated an overview of the characteristics of CAR T-cell clinical development in the United States, Canada and Europe. Subsequently, the characteristics of clinical trials with CAR T-cell products that proceeded to a subsequent clinical trial, used as a proxy for success, were compared with those that did not proceed.


      From the U.S. and European Union clinical trial databases, 106 CAR T-cell trials were selected, from which 49 were linked to a subsequent trial and 57 were not. The majority of the trials had an academic sponsor from which most did not proceed, whereas most commercially sponsored trials were followed by another clinical trial. Furthermore, trials with a subsequent trial more frequently recruited large patient cohorts and were more often multicenter compared with trials that were not followed up.


      These characteristics can be used by investigators to better design clinical trials with CAR T cells. We encourage sponsors to plan clinical development ahead for a higher efficiency of product development and thereby achieving a higher success rate of development towards MAA.

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        • de Wilde S.
        • Guchelaar H.-J.
        • Zandvliet M.L.
        • Meij P.
        Clinical development of gene- and cell-based therapies: overview of the European landscape.
        Mol Ther Methods Clin Dev. 2016; 3: 16073
        • Maciulaitis R.
        • D'Apote L.
        • Buchanan A.
        • Pioppo L.
        • Schneider C.K.
        Clinical development of advanced therapy medicinal products in Europe: evidence that regulators must be proactive.
        Mol Ther. 2012; 20: 479-482
        • Feigal E.G.
        • Tsokas K.
        • Viswanathan S.
        • Zhang J.
        • Priest C.
        • Pearce J.
        • et al.
        Proceedings: international regulatory considerations on development pathways for cell therapies.
        Stem Cells Transl Med. 2014; 3: 879-887
        • Ecorys Nederland B.V.
        • University Utrecht
        Study on the regulation of advanced therapies in selected jurisdictions.
        • European Medicines Agency
        CAT monthly report of application procedure, guidelines and related documents on advanced therapies.
        (Monthly report CAT September 2016—WC500213010.pdf; Available from:) ([Accessed 4 October 2016])
        • Fischbach M.A.
        • Bluestone J.A.
        • Lim W.A.
        Cell-based therapeutics: the next pillar of medicine.
        Sci Transl Med. 2013; 5: 179ps7
        • Kim M.-G.
        • Kim D.
        • Suh S.-K.
        • Park Z.
        • Choi M.J.
        • Oh Y.-K.
        Current status and regulatory perspective of chimeric antigen receptor-modified T cell therapeutics.
        Arch Pharm Res. 2016; 39: 437-452
        • Dübel S.
        • Reichert J.M.
        Handbook of therapeutic antibodies.
        2nd ed. Wiley-Blackwell, Weinheim, Germany2014
        • Jackson H.J.
        • Rafiq S.
        • Brentjens R.J.
        Driving CAR T-cells forward.
        Nat Rev Clin Oncol. 2016; 13: 370-383
        • Geyer M.B.
        • Brentjens R.J.
        Review: current clinical applications of chimeric antigen receptor (CAR) modified T cells.
        Cytotherapy. 2016;
        • de Wilde S.
        • Veltrop-Duits L.
        • Hoozemans-Strik M.
        • Ras T.
        • Blom-Veenman J.
        • Guchelaar H.-J.
        • et al.
        Hurdles in clinical implementation of academic advanced therapy medicinal products: a national evaluation.
        Cytotherapy. 2016; 18: 797-805
        • Wang X.
        • Rivière I.
        Clinical manufacturing of CAR T cells: foundation of a promising therapy.
        Mol Ther Oncol. 2016; 3: 16015
        • Lawrence S.
        UPDATED: FDA halts Juno CAR-T trial after three patient deaths | FierceBiotech.
        (Available from:) ([Accessed 12 August 2016])
        • Herper M.
        Novartis dissolves CAR-T unit, cutting 120 positions.
        Forbes. 2016
      1. Kite Pharma Initiates Rolling Submission of U.S. Biologics License Application (BLA) for KTE-C19, its investigational anti-CD19 CAR-T therapy, for the treatment of patients with relapsed/refractory aggressive B-cell Non-Hodgkin Lymphoma (NHL) | Business Wire.
        (Available from:) ([Accessed 29 January 2017])
        • de Wilde S.
        • Guchelaar H.-J.
        • Herberts C.
        • Lowdell M.
        • Hildebrandt M.
        • Zandvliet M.
        • et al.
        Development of cell therapy medicinal products by academic institutes.
        Drug Discov Today. 2016;
        • Detela G.
        Summary review on ATMPs approved in the EU.
        Catapult. 2016 (Available from:) ([Accessed 15 September 2016])
        • Hourd P.
        • Chandra A.
        • Medcalf N.
        • Williams D.J.
        Regulatory challenges for the manufacture and scale-out of autologous cell therapies.
        Harvard Stem Cell Institute, 2014
        • Appel L.J.
        A primer on the design, conduct, and interpretation of clinical trials.
        Clin J Am Soc Nephrol. 2006; 1: 1360-1367