Ann Lab Med.  2024 Jul;44(4):314-323. 10.3343/alm.2023.0382.

Manufacturing Cell and Gene Therapies: Challenges in Clinical Translation

• Lee NK
• Chang JW

• KMID: 2557930
• DOI: http://doi.org/10.3343/alm.2023.0382

Abstract

The safety and efficacy of both cell and gene therapies have been demonstrated in numerous preclinical and clinical trials. Chimeric antigen receptor T (CAR-T) cell therapy, which leverages the technologies of both cell and gene therapies, has also shown great promise for treating various cancers. Advancements in pertinent fields have also highlighted challenges faced while manufacturing cell and gene therapy products. Potential problems and obstacles must be addressed to ease the clinical translation of individual therapies. Literature reviews of representative cell-based, gene-based, and cell-based gene therapies with regard to their general manufacturing processes, the challenges faced during manufacturing, and QC specifications are limited. We review the general manufacturing processes of cell and gene therapies, including those involving mesenchymal stem cells, viral vectors, and CAR-T cells. The complexities associated with the manufacturing processes and subsequent QC/validation processes may present challenges that could impede the clinical progression of the products. This article addresses these potential challenges. Further, we discuss the use of the manufacturing model and its impact on cell and gene therapy.

Keyword

Cell therapy; Chimeric antigen receptor T; Clinical translation; Gene therapy; Manufacturing; Mesenchymal stem cells; Viral vectors

Figure

• 

  Fig. 1 Cell and gene therapy manufacturing processes. Black boxes represent the flow diagram for MSC-based cell therapy. Gray boxes denote the flow diagram for CAR-T cell-based gene therapy. The process flows for LV- and AAV-based gene therapies are indicated in white boxes with solid lines. Plasmid production and purification are indicated in white boxes with dashed lines. Abbreviations: MSC, mesenchymal stem cell; CAR-T, chimeric antigen receptor T; LV, lentiviral vector; AAV, adeno-associated virus; DF, diafiltration; UF, ultrafiltration.

Reference

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