Allogeneic cell therapy is poised to be the next generation of anti-tumor cell therapy due to multiple advantages, including the availability of a wide range of cell sources from healthy donors, the ability to produce larger batch sizes and more consistent generation of the final product, and minimal immune responses. Lymphocytes and T-cells have dominated the cell therapy landscape; however, natural killer (NK) cells have shown potential for the treatment of blood cancers and solid tumors. Century Therapeutics has developed a platform capable of generating induced pluripotent stem cell (iPSC)-derived natural killer (iNK) cells for therapeutic applications. With the unlimited differentiation potential of iPSC, the generation of hematopoietic progenitor cells (HPC) provides a robust intermediate that allows for reproducible and reliable starting materials for the large-scale manufacturing of iNK cells as a cell therapy product.<br/>To ensure the robustness and quality of our final iNK drug product, we systematically developed processes for cell manufacturing, pre-activation, freezing, and drug product storage. Throughout this development, we identified multiple attributes, such as cell yield, viability, cellular phenotype, cell health and cell functionality, to assess and control product quality. We evaluated the margin of pre-cryopreservation process duration to ensure the manufacturing process is acceptable to minimize the effect on cell quality of the drug substance and final drug product. An integral element of the cryopreservation process is the assessment of raw materials e.g., cryoprotectants (CPA), that are suitable for iNK. Additional efforts were placed on the freezing steps, which included the use of slow-cooling freezer containers and controlled-rate freezers to ensure consistent and reproducible cell freezing profiles. To further access the product quality, we established analytical strategies to explore the cell health and functionality. Our results highlight the establishment of a robust and consistent process to enable clinically-relevant manufacture of Century’s allogeneic iPSC-derived NK cell therapies.

Cryopreservation of induced pluripotent stem cell-derived natural killer cells for off-the-shelf cell therapy

ACS Spring 2022

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