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Production of Clinical T Cell Therapies

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Developments in T Cell Based Cancer Immunotherapies

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The improving effectiveness of adoptive T cell therapies has led to their increased clinical application. Most of these adoptive T cell therapies are being produced in small lots in cell therapy centers affiliated with or located within academic health centers. Typically, the cells are produced from autologous or HLA compatible donors and one lot is used for a single patient. As part of early phase clinical trials, the best available methods and devices for the manufacture of clinical grade T cell therapies are described. For most adoptive T cell therapies the starting material is a peripheral blood mononuclear cell (PBMC) product that is collected by apheresis using closed system blood cell separators. Many manufacturing processes require that red blood cells be removed from the PBMCs or that T cells or T cell subsets are isolated. Classically, T cells have been cultured in flasks, but culture in closed systems which reduces the risk of microbial contamination is desirable and bags and bioreactors are often used for T cell culture and expansion. T cell culture involves growth and expansion in media supplemented with serum, cytokines and feeder cells or other artificial stimulators, i.e. anti-CD3/28 beads or K562 cell line. Recently, closed system transduction methods have been developed that can be used to produce genetically engineered T cells. Automated instruments are available to wash and concentrate products. The final product is assessed for the quantity of cells present, purity, sterility and potency. The use of these best practices is allowing for the consistent manufacturing of high quality cellular therapies to support early phase clinical trials.

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Author information

Authors and Affiliations

  1. Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, 10 Center Drive – MSC-1184, Building 10, Room 1C711, Bethesda, MD, 20892-1184, USA

    David Stroncek M.D., Jianjian Jin, Virginia David-Ocampo, Vicki Fellowes & Larry Moses

  2. Kite Pharma, Inc., Santa Monica, CA, USA

    Marianna Sabatino

Authors
  1. David Stroncek M.D.
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  2. Jianjian Jin
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  3. Virginia David-Ocampo
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  4. Vicki Fellowes
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  5. Larry Moses
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  6. Marianna Sabatino
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Corresponding author

Correspondence to David Stroncek M.D. .

Editor information

Editors and Affiliations

  1. Unit of Melanoma & Cancer Immunotherapy, National Tumor Institute Fondazione G., Naples, Italy

    Paolo A. Ascierto

  2. Department of Transfusion Medicine, National Institutes of Health, Bethesda, Maryland, USA

    David F. Stroncek

  3. Department of Transfusion Medicine, National Institutes of Health, BETHESDA, Maryland, USA

    Ena Wang

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Stroncek, D., Jin, J., David-Ocampo, V., Fellowes, V., Moses, L., Sabatino, M. (2015). Production of Clinical T Cell Therapies. In: Ascierto, P., Stroncek, D., Wang, E. (eds) Developments in T Cell Based Cancer Immunotherapies. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-21167-1_6

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  • DOI: https://doi.org/10.1007/978-3-319-21167-1_6

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-21166-4

  • Online ISBN: 978-3-319-21167-1

  • eBook Packages: MedicineMedicine (R0)

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