Cell therapy firms need to think about freezing earlier in process development according to an expert, who says optimized cryopreservation is key.

Cell therapies have the potential to revolutionize medicine. For example, products like Yescarta and Kymriah can treat cancers more effectively and with fewer side effects than even the best chemotherapies.

But unlike chemotherapies, cell therapies are highly susceptible to the temperature fluctuations that occur during transportation.

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To address this, developers protect their products using various methods, with cryopreservation being a common approach for single cell therapies.

The general idea is to freeze the therapy at the lab, deliver it to the clinic and thaw it for administration to the patient.

While freeze-thawing is effective, almost all areas of the cryopreservation process could be improved says researcher Charles Hunt.

Optimization

In June, Hunt argued that “optimising cryopreservation is as important as optimisation of the cell culture process” in a paper in the journal Transfusion Medicine and Hemotherapy.

Hunt – who was previously operations manager at UK Stem cell Bank – told Bioprocess Insider that “perhaps the biggest challenge is to translate the knowledge held within the cryobiology community into the cell therapy industry where for too long cryopreservation has been an often poorly understood afterthought in the cell manufacturing process.

“Cryopreservation has often taken a back seat to other areas of bioprocessing, such that it has been identified as a potential bottleneck in the development of cellular therapy products going forward” he said.

Hunt added that, “sub-optimal cryopreservation not only reduces cell viability but can also lead to batch-to-batch variability and potentially to genetic and epigenetic changes that may compromise the production process, while adverse storage conditions may reduce the effectiveness of the end-product.”

Supercooling

Hunt suggested the cell therapy sector would benefit from better knowledge of the freezing process.

“One area that has received little attention is the control of the ice nucleation event and the degree of supercooling experienced by the system before ice nucleates.

“This is a little investigated phenomenon that has been shown to affect viability through a number of mechanisms. Reliable methods to control supercooling in cellular therapies are only now being investigated,” he said.

Transportation conditions also need to be more of a focus for the cell therapy industry according to Hunt.

“During storage and transportation the challenges reflect the need to maintain a steady and low sub-zero temperature to avoid the growth of ice crystals and the deleterious effects of high solute concentration in the milieu surrounding the frozen cells.”