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Toward precision manufacturing of immunogene T-cell therapies

  • Jun Xu
    Affiliations
    Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
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  • J. Joseph Melenhorst
    Affiliations
    Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
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  • Joseph A. Fraietta
    Correspondence
    Correspondence: Joseph A. Fraietta, PhD, Perelman Center for Advanced Medicine South Tower (SPE-9), Room 104, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104-5156, USA.
    Affiliations
    Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
    Search for articles by this author
Published:April 10, 2018DOI:https://doi.org/10.1016/j.jcyt.2017.12.007

      Abstract

      Cancer can be effectively targeted using a patient's own T cells equipped with synthetic receptors, including chimeric antigen receptors (CARs) that redirect and reprogram these lymphocytes to mediate tumor rejection. Over the past two decades, several strategies to manufacture genetically engineered T cells have been proposed, with the goal of generating optimally functional cellular products for adoptive transfer. Based on this work, protocols for manufacturing clinical-grade CAR T cells have been established, but these complex methods have been used to treat only a few hundred individuals. As CAR T-cell therapy progresses into later-phase clinical trials and becomes an option for more patients, a major consideration for academic institutions and industry is developing robust manufacturing processes that will permit scaling-out production of immunogene T-cell therapies in a reproducible and efficient manner. In this review, we will discuss the steps involved in cell processing, the major obstacles surrounding T-cell manufacturing platforms and the approaches for improving cellular product potency. Finally, we will address the challenges of expanding CAR T-cell therapy to a global patient population.

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