From production to patient: challenges and approaches for delivering cell therapies

Gene-modified, cell-based therapies—an overview

“…In the last several years, the cell therapy industry has grown in scale, being adopted in many countries and institutions, and collecting revenues in excess of a billion dollars [2]. Although challenges remain [3], cell therapy is poised to make an ever increasing impact on malignant and degenerative diseases hitherto untreatable with current management. Much of this development demands the creation of gene-modified cells, now made more accessible to the clinic through improved editing and vector delivery platforms.…”

“…Cells possess unique risk profiles compared to drugs and biologics, and their biological properties require a more comprehensive preclinical safety program before they are infused. Such a program will be cell product-specific, and will need to account for the different risks in these products [3]. The regulatory environment should be structured in a way that discriminates favorably well-validated innovations, from sham technologies that promote medical tourism.…”

“…Continued dialogue between innovators and regulators is needed to push these therapies forward. Finally, the ultimate translation of most promising gene-modified cell therapy protocols require well characterized processes that take into account the difficulties in deciding the optimal manufacture of the cells, processing at different sites, transportation, and cryopreservation of these products [3]. In the last 2 decades the field of gene modified cell therapy has emerged from theory into practice.…”

The role of biopreservation in cell and gene therapy bioprocessing

“…Freezing is the most common biopreservation method employed in CGT processes [2], with the first successful cryopreservation taking place in 1949 with spermatozoa in glycerol [10].…”

“…This can uncouple the expansion and/or manipulation of cells from the clinic, creating product shelf-life and facilitates the transport/storage of any product intermediates (e.g. newly isolated cells or even viral vectors) too [2] Fig 1. Indeed, where the process necessitates transfer of cellular material from the clinic to an off-site facility for processing and/or expansion, biopreservation measures will be critical to product quality and success. This places particular emphasis on the appropriate selection of biopreservation methods, with a need to demonstrate that they do not adversely impact the product's CQAs.…”