Design and implementation of adoptive therapy with chimeric antigen receptor-modified T cells


  • Michael C. Jensen,

    1. Seattle Children's Research Institute, University of Washington, Seattle, WA, USA
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  • Stanley R. Riddell

    Corresponding author
    1. Program in Immunology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA
    • Correspondence to:

      Stanley R. Riddell


      Fred Hutchinson Cancer Research Center

      1100 Fairview Avenue N.

      Seattle, WA 98109, USA

      Tel.: +1 206 667 5249

      Fax: +1 206 667 7983


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This article is corrected by:

  1. Errata: Corrigendum Volume 258, Issue 1, 259, Article first published online: 11 February 2014


A major advance in adoptive T-cell therapy (ACT) is the ability to efficiently endow patient's T cells with reactivity for tumor antigens through the stable or regulated introduction of genes that encode high affinity tumor-targeting T-cell receptors (TCRs) or synthetic chimeric antigen receptors (CARs). Case reports and small series of patients treated with TCR- or CAR-modified T cells have shown durable responses in a subset of patients, particularly with B-cell malignancies treated with T cells modified to express a CAR that targets the CD19 molecule. However, many patients do not respond to therapy and serious on and off-target toxicities have been observed with TCR- and CAR-modified T cells. Thus, challenges remain to make ACT with gene-modified T cells a reproducibly effective and safe therapy and to expand the breadth of patients that can be treated to include those with common epithelial malignancies. This review discusses research topics in our laboratories that focus on the design and implementation of ACT with CAR-modified T cells. These include cell intrinsic properties of distinct T-cell subsets that may facilitate preparing therapeutic T-cell products of defined composition for reproducible efficacy and safety, the design of tumor targeting receptors that optimize signaling of T-cell effector functions and facilitate tracking of migration of CAR-modified T cells in vivo, and novel CAR designs that have alternative ligand binding domains or confer regulated function and/or survival of transduced T cells.