Manufacturing Cell and Gene Therapies: Challenges in Clinical Translation

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.

Towards a Cure for Diamond–Blackfan Anemia: Views on Gene Therapy

“…Additionally, HSCT continues to present significant challenges, including its high cost, inherent safety concerns, variability in efficacy, and manufacturing difficulties. A key challenge lies in the production of therapeutic agents at high titers and with consistent quality [ 84 ].…”