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


ABSTRACT: 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.

SUBMITTER: Song HW 

PROVIDER: S-EPMC9815724 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

Song Hannah W HW   Somerville Robert P RP   Stroncek David F DF   Highfill Steven L SL  

International reviews of immunology 20220429 6


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  ...[more]

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