Scaling up and scaling out: Advances and challenges in manufacturing engineered T cell therapies

Engineered T cell therapies such as CAR-T cells and TCR-T cells have generated impressive patient responses in previously incurable diseases. In the past few years there have been a number of technical innovations that enable robust clinical manufacturing in functionally closed and often automated s...

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Published inInternational reviews of immunology Vol. 41; no. 6; pp. 638 - 648
Main Authors Song, Hannah W., Somerville, Robert P., Stroncek, David F., Highfill, Steven L.
Format Journal Article
LanguageEnglish
Published England Taylor & Francis 2022
Subjects
B-Lymphocytes
CAR T cells
Cell Therapy
GMP manufacturing
Humans
Immunotherapy, Adoptive
Neoplasms - therapy
Process development
Receptors, Antigen, T-Cell - genetics
T-Lymphocytes
TCR T cells
Process development
CAR T cells
Cell Therapy
GMP manufacturing
TCR T cells
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Summary:Engineered T cell therapies such as CAR-T cells and TCR-T cells have generated impressive patient responses in previously incurable diseases. In the past few years there have been a number of technical innovations that enable robust clinical manufacturing in functionally closed and often automated systems. Here we describe the latest technology used to manufacture CAR- and TCR-engineered T cells in the clinic, including cell purification, transduction/transfection, expansion and harvest. To help compare the different systems available, we present three case studies of engineered T cells manufactured for phase I clinical trials at the NIH Clinical Center (CD30 CAR-T cells for lymphoma, CD19/CD22 bispecific CAR-T cells for B cell malignancies, and E7 TCR T cells for human papilloma virus-associated cancers). Continued improvement in cell manufacturing technology will help enable world-wide implementation of engineered T cell therapies.
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ISSN:0883-0185
1563-5244
1563-5244
DOI:10.1080/08830185.2022.2067154