Ultra-Low Temperature Freezers (ULTs) can make an important contribution in the field of cell and gene therapies. For a long time, complex cryopreservation with liquid nitrogen was the standard for freezing all therapeutic substances. However, studies show that some cell and gene therapy products remain stable even in ULTs at around -80 C°. With ULTs, medical facilities have another cold chain solution that can be used alongside cryogenic freezers.
Thanks to major advances in the field of stem cell research in recent years, it is now possible to multiply and reprogram cells. People with hereditary or chronic diseases in particular benefit from this, as novel cell and gene therapies are achieving ever greater success. Increasingly, diseases that just a few years ago were considered insurmountable can now be treated: these include several severe immune defects, retinal diseases, beta thalassemia and some neuromuscular diseases. Even patients suffering from diseases such as cancer, cystic fibrosis, Alzheimer’s, diabetes, Parkinson’s, or rheumatism can now find hope thanks to the innovative therapies. During these therapies, so-called transformative treatments are applied.
For the genetic material to fully develop its therapeutic effect in the patient, it must be stored at constantly low temperatures almost continuously during its supply chain process. So far, the so-called cryopreservation has mainly been used for this purpose. In this method, the cell and gene therapy products are frozen at a temperature of -196 °C using liquid nitrogen. However, cryopreservation is a very complex and expensive procedure that can limit the availability of these advanced therapies to only a small number of patients who need them. Nevertheless, recent studies have shown that numerous substances can remain stable even at temperatures around -86 °C, temperatures that can be reached easily and reliably with good Ultra-Low Freezers (ULTs). These devices thus represent an easy-to-use and economical option for medical institutions to preserve certain cell and gene therapy products, contributing to the wider adoption of these novel therapies.
How do cell and gene therapies work?
Both cell and gene therapy approaches involve modifying genetic material to improve how certain cells work or fight a certain disease. Diseases are analyzed at the molecular level with the aim of replacing damaged or dysfunctional molecules.
In cell therapy, whole cells are taken from a person and are modified genetically in a laboratory. These cells can be taken from the patient (autologous cells) or from a donor (allogeneic cells), and when the cells have been processed, they are then administered to the patient and take effect. There are around 200 different cell types in the human body – each of which has very specific functions. However, according to current knowledge, not all of them are suitable for cell therapy. Cells that can be used in this therapy are for example haematopoietic stem cells (blood stem cells), mesenchymal stem cells (connective tissue cells), embryonic stem cells, induced pluripotent stem cells and immune defense cells.
In gene therapy, genes are the target. Gene therapy involves direct intervention in the genome of the body’s cells. This can be done in several ways, but the most common one employs vectors such as viruses to transport a specific piece of genetic material to target cells and then facilitate its entry through the membrane. Once this happens, the cells’ proteins and enzymes incorporate the new genetic material into their own genome, which can have different effects. For example, the new piece of DNA is used as a blueprint for the production of certain proteins that the patient would otherwise not be able to produce himself, or it could can stimulate the production of certain proteins that the patient’s body may already be producing, but only in small amounts until then. Another possibility would be for the new genetic material to be used to block the expression (production) of a specific protein that is causing problems in the patient’s body.
Different substances require different temperatures
For these cell or gene therapy substances to remain intact and effective, they must be stored and transported at very low temperatures. Materials require intense refrigeration from their collection in a clinical setting, their transport to a processing center, and right through the return to the clinic and their administration. A question with practical and economic consequences, however, is how low does the storage temperature need to be.
In one study, storage of alginate-encapsulated liver cell spheroids at -80°C led to a rapid deterioration in functional recovery after just a few weeks. When stored in this way, embryonic stem cells also lost their viability and exhibited altered properties. This shows that there are biologicals for which there is no alternative to cryopreservation.
However not all specimens require are like this. In another study, the stability of peripheral blood stem cells (PSBCs) both after storage in liquid nitrogen and in ULTs was compared: after five years, there were hardly any differences in the cells. In addition, after storage for more than 1.5 years at – 80°C, PBSCs yielded good recovery rates after autologous transplantation. And studies comparing the response of dental pulp stem cells and pancreatic islets to freezing at -85°C and -196°C found no loss of differentiation ability and functionality of the cell samples after more than six months storage at either temperature.
ULTs can be an efficient, reliable, and economical alternative
Efficient ultra-low freezers able to reach a temperature of -86°C appear to be a potential alternative to the storage of some cell and gene therapy products in liquid nitrogen. Freezing the materials using ULTs is much easier than with classic cryopreservation, and these medical devices have therefore the potential to contribute to improved and more economical processes in cell and gene therapies.
ULTs from leading suppliers such as B Medical Systems only use natural refrigerants with high cooling efficiency. The units are made of high-quality stainless steel and come with a password-protected door-locking mechanism, insulated inner doors, sealed gaskets, and reinforced frames to ensure minimal cold air loss or the onset of freezing. In addition, their reliability is significantly increased by add-ons such as emergency power supplies, an audiovisual alarm system, and a remote monitoring, reporting and long-term logging of data system that can provide notifications of temperature changes via both SMS and email.
In principle, cell and gene therapies are still in the early stages of development, but they have enormous potential. In the future, cell and gene therapies could enable much more targeted, personalized treatment and finally conquer diseases that were previously considered incurable. Around 20 new cell and gene therapy products are currently expected to be approved each year by 2025, and ULTs could be the solutions that many medical institutions need to efficiently employ such therapies. These devices are therefore becoming of great importance to ensure that such therapies will reach as many patients as possible more easily and economically, paving the way for a new chapter in the history of medicine.
Author: Marnick Dewilde, Chief Sales Officer Medical Refrigeration and Blood Management Solutions at B Medical Systems.