Hannah W Song, Robert P Somerville, David F Stroncek, Steven L Highfill
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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 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.
期刊介绍:
This review journal provides the most current information on basic and translational research in immunology and related fields. In addition to invited reviews, the journal accepts for publication articles and editorials on relevant topics proposed by contributors. Each issue of International Reviews of Immunology contains both solicited and unsolicited review articles, editorials, and ''In-this-Issue'' highlights. The journal also hosts reviews that position the authors'' original work relative to advances in a given field, bridging the gap between annual reviews and the original research articles.
This review series is relevant to all immunologists, molecular biologists, microbiologists, translational scientists, industry researchers, and physicians who work in basic and clinical immunology, inflammatory and allergic diseases, vaccines, and additional topics relevant to medical research and drug development that connect immunology to disciplines such as oncology, cardiovascular disease, and metabolic disorders.
Covered in International Reviews of Immunology: Basic and developmental immunology (innate and adaptive immunity; inflammation; and tumor and microbial immunology); Clinical research (mechanisms of disease in man pertaining to infectious diseases, autoimmunity, allergy, oncology / immunology); and Translational research (relevant to biomarkers, diagnostics, vaccines, and drug development).