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.
Graphical Abstract
Acknowledgements
We thank the staff of the Center for Cellular Engineering, Department of Transfusion Medicine (NIH Clinical Center) for manufacture and characterization of T cells therapies. We would like to thank Dr. James Kochenderfer (Surgery Branch, NIH Clinical Center), Dr. Nirali Shah (Pediatric Oncology Branch, NIH Clinical Center), and Dr. Christian Hinrichs (Rutgers Cancer Institute) for support in the development of the clinical protocols for CD30 CAR, CD19/CD22 Bispecific CAR, and E7 TCR T cells, respectively.
Declaration of interest
The authors declare that they have no conflict of interest.
The opinions expressed in this article are the author’s own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government.