The cell therapy industry is enjoying a period of unprecedented growth. The number of cell-based treatments transitioning from development to commercial manufacturing is forecast to continue growing dramatically over the next decade. This predicted growth rate can only be maintained by a parallel increase in the availability of therapeutic starting materials.
Developers are increasingly turning to isolated immune cells as their primary starting material, cutting the time and resources spent on purifying and characterizing specific cell populations. Leukapheresis material collected from donors must be processed using density gradient separation and flow cytometry techniques to isolate target cell types before storage or shipping to the customer. Cryopreservation is also a critical and nearly universal step in the processing of these isolated immune cell populations. It is a practical necessity for maintaining viability and function over long-term storage and long-distance shipping, and beneficial in terms of safeguarding both consistency and availability.
SAFEGUARDING IMMUNE CELL QUALITY
Reliable immune cell quality is key to the success of any immunotherapy product. It is well-established that living cells are exquisitely vulnerable to their environment, as well as capable of altering their phenotype and functionality in response to culture and storage conditions. Safeguarding quality is not simply a matter of preserving viability, although that is undoubtedly part of it. But the quality of any cellular therapy product is just as dependent on maintaining therapeutic efficacy–the specific functional characteristics of a cell type that lend it value.
Many different factors impact immune cell viability and function. Leukapheresis collection methods and expertise impact cell yield and viability. The presence of various cytokines and growth factors in cell culture media during growth and expansion can promote one cell type over another. Granulocyte contamination and length of storage time impact cell health and functionality, as well as the relative number and type of immune cells present.  Cell isolation methods should be optimized, with stringent quality oversight to ensure best practices are consistently followed.
Cryopreservation is by far one of the most critical factors governing therapeutic cell quality. Temperature excursions outside of an optimal range impact cell health, which is why cryopreservation methods, freezing media, and cell thawing methods must be optimized.
In the wrong hands, cryopreservation can result in a dramatic loss of cell viability and/or function, and for that reason, scientists have historically been wary of using cryopreserved products. HemaCare has spent the last decade perfecting its cryopreservation protocols to ensure maximum viability and functionality:
- Industry leading cryopreservation expertise.
- On-site immune cell collections with multiple collection sites.
- Same-day cell processing, isolation, and cryopreservation.
- Optimized procedures using GMP-compliant freezing media and rate-controlled cryopreservation techniques to ensure optimal cell viability and recovery.
- Cryopreserved cells have >95% viability measured by flow cytometry, with guaranteed cell counts.
- Well-integrated workflows designed to minimize room temperature exposure and freeze-thaw cycles.
When done right, cryopreservation simplifies shipping and storage logistics while maintaining cell quality. It also helps ensure product consistency.
MANAGING STARTING MATERIAL VARIABILITY
Freshly isolated cellular material is often considered the gold standard of quality. Freshly isolated cells are considered preferable in clinical situations where autologous treatments are collected and administered at the same facility or when shipping and storage time are expected to be minimal. However, it is important to remember that quality can be conditional.
Freshly isolated starting material degrades over time; generally speaking, cells exposed to more than 8 hours of shipping and storage time at room temperature will experience a decline in viability and/or functionality.  The quality of fresh material varies relative to the length of time between collection and processing, and the length of time between shipping and receiving.
Product variability is one of the top concerns of the cell therapy industry.  The success of any pharmaceutical product lies in that product being consistently safe and effective. However, cell-based therapeutics are intrinsically variable from the start because the cells used for these therapies are derived from individual donors who are inherently different. Therefore, minimizing variability means optimizing and standardizing what can be controlled–raw material sourcing, cell processing, handling methods, and quality oversight. Cryopreservation is an important tool for managing starting material variability.  Cryopreserving isolated immune cells that will be used as cell therapy starting materials locks in viability and potency and ensures consistency across multiple treatments derived from the same cell collection.
The COVID-19 pandemic taught the cell therapy industry crucial lessons. The availability of donor-derived starting materials is not necessarily guaranteed. Even large donor networks cannot always compensate for complex adverse events. Cryopreserved products helped save the cell therapy industry when fresh material sourcing became a challenge. As the cell therapy industry grows, cryopreservation can help simplify complex logistics, maintain product stability, and ensure product consistency to support scale up.
HemaCare cryopreservation expertise guarantees optimized processes and products. Our quality oversight means that our customers can always expect consistent high-performance products. For more information on ordering our isolated immune cell products, please visit our website.
- McKenna K. C., et al. Delayed processing of blood increases the frequency of activated CD11b+ CD15+ granulocytes which inhibit T cell function. J Immunol Methods. 341(1-2):68-75. Feb 2009.
- Clarke D. et al. Ensuring source material consistency and continuity for commercialization of advanced therapies. Cell and Gene Therapy Insights. April 2020.
- Juhl M., et al. Cryopreservation of peripheral blood mononuclear cells for use in proliferation assays: First step towards potency assays. Journal of Immunological Methods. 488. Jan 2021.