Highlights
- •Preservation technology is essential to the supply chain of cellular therapy.
- •Five factors in cryopreservation affect the outcome of a cell therapy.
- •DMSO is the most commonly used CPA to freeze cells in cell-based immunotherapy.
- •The most commonly used cooling rate is -1˚C/min to freeze cells for immunotherapy.
- •Non-DMSO CPAs have demonstrated to be better than DMSO at preserving immune cells.
Abstract
In the unique supply chain of cellular therapies, preservation is important to keep
the cell product viable. Many factors in cryopreservation affect the outcome of a
cell therapy: (i) formulation and introduction of a freezing medium, (ii) cooling
rate, (iii) storage conditions, (iv) thawing conditions and (v) post-thaw processing.
This article surveys clinical trials of cellular immunotherapy that used cryopreserved
regulatory, chimeric antigen receptor or gamma delta T cells, dendritic cells or natural
killer (NK) cells. Several observations are summarized from the given information.
The aforementioned cell types have been similarly frozen in media containing 5–10%
dimethyl sulfoxide (DMSO) with plasma, serum or human serum albumin. Two common freezing
methods are an insulated freezing container such as Nalgene Mr. Frosty and a controlled-rate
freezer at a cooling rate of -1°C/min. Water baths at approximately 37°C have been
commonly used for thawing. Post-thaw processing of cryopreserved cells varied greatly:
some studies infused the cells immediately upon thawing; some diluted the cells in
a carrier solution of varying formulation before infusion; some washed cells to remove
cryoprotective agents; and others re-cultured cells to recover cell viability or functionality
lost due to cryopreservation. Emerging approaches to preserving cellular immunotherapies
are also described. DMSO-free formulations of the freezing media have demonstrated
improved preservation of cell viability in T lymphocytes and of cytotoxic function
in natural killer cells. Saccharides are a common type of molecule used as an alternative
cryoprotective agent to DMSO. Improving methods of preservation will be critical to
growth in the clinical use of cellular immunotherapies.
Key Words
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Article info
Publication history
Published online: August 12, 2019
Accepted:
July 22,
2019
Received:
July 3,
2019
Identification
Copyright
© 2019 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.
