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Expansion, Purification, and Functional Assessment of Human Peripheral Blood NK Cells
Published on: February 2, 2011
David H McKenna1, Darin Sumstad, Nancy Bostrom
1Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, University of Minnesota Medical School, Minnesota 55108, USA. mcken020@umn.edu
Background:
Natural killer (NK) cells, a subset of lymphocytes and part of the innate immune system, play a crucial role in defense against cancer and viral infection. Herein is a report on the experience of clinical-scale, good manufacturing practices (GMPs) production of NK cells to treat advanced cancer.
Study Design And Methods:
Two types of NK cell enrichments were performed on nonmobilized peripheral blood mononuclear cell apheresis collections with a cell selection system (CliniMACS, Miltenyi): CD3 cell depletion to enrich for NK cells and CD3 cell depletion followed by CD56 cell selection to obtain a more pure NK cell product. After overnight incubation with interleukin-2 (IL-2), cells were washed, resuspended in 5 percent human serum albumin, and then released for infusion.
Results:
A total of 70 NK cell therapy products have been manufactured for patient infusion since 2000. For the CD3 cell-depleted NK cell products, the mean purity, recovery, and viability were 38, 79, and 86 percent, respectively. For the CD3 cell-depleted/CD56 cell-enriched NK cell products, the mean purity, recovery, and viability were 90, 19, and 85 percent, respectively. Gram stain, sterility, and endotoxin testing were all within acceptable limits for established lot release. Compared to the resting processed cells, IL-2 activation significantly increased the function of cells in cytotoxicity assays.
Conclusion:
Clinical-scale production of NK cells is efficient and can be performed under GMPs. The purified NK cell product results in high NK cell purity with minimal contamination by T cells, monocytes, and B cells, but it requires more time for processing and results in a lower NK cell recovery when compared to NK cell enrichment with CD3 cell depletion alone. Additional laboratory studies and results from clinical trials will identify the best source and type of NK cell product.
Insights
Clinical-scale production of natural killer (NK) cells for cancer therapy is feasible under Good Manufacturing Practices (GMPs). While purification yields high-purity NK cells, it reduces recovery compared to simpler enrichment methods.
Area of Science:
- Immunology
- Cell Therapy
- Oncology
Background:
- Natural killer (NK) cells are crucial innate immune cells for fighting cancer and viral infections.
- Clinical-scale production of NK cells under Good Manufacturing Practices (GMPs) is explored for advanced cancer treatment.
Purpose of the Study:
- To report on the experience of clinical-scale GMP production of NK cells for cancer therapy.
- To evaluate different NK cell enrichment methods for purity, recovery, and viability.
Main Methods:
- Two NK cell enrichment methods were used: CD3 cell depletion and CD3 depletion followed by CD56 selection.
- Cells were incubated with interleukin-2 (IL-2) and processed for infusion under GMP conditions.
Main Results:
- 70 NK cell products were manufactured. CD3/CD56 selection yielded 90% purity but only 19% recovery, while CD3 depletion alone gave 38% purity and 79% recovery.
- All products met lot release criteria for sterility and endotoxins. IL-2 activation enhanced NK cell cytotoxic function.
Conclusions:
- Clinical-scale NK cell production under GMPs is efficient.
- Purified NK cells offer high purity but lower recovery; further studies will optimize NK cell source and product type.
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