[PDF][PDF] Generation of “off-the-shelf” natural killer cells from peripheral blood cell-derived induced pluripotent stem cells

J Zeng, SY Tang, LL Toh, S Wang - Stem cell reports, 2017 - cell.com
J Zeng, SY Tang, LL Toh, S Wang
Stem cell reports, 2017cell.com
Current donor cell-dependent strategies can only produce limited" made-to-order"
therapeutic natural killer (NK) cells for limited patients. To provide unlimited" off-the-shelf"
NK cells that serve many recipients, we designed and demonstrated a holistic manufacturing
scheme to mass-produce NK cells from induced pluripotent stem cells (iPSCs). Starting with
a highly accessible human cell source, peripheral blood cells (PBCs), we derived a good
manufacturing practice-compatible iPSC source, PBC-derived iPSCs (PBC-iPSCs) for this …
Summary
Current donor cell-dependent strategies can only produce limited "made-to-order" therapeutic natural killer (NK) cells for limited patients. To provide unlimited "off-the-shelf" NK cells that serve many recipients, we designed and demonstrated a holistic manufacturing scheme to mass-produce NK cells from induced pluripotent stem cells (iPSCs). Starting with a highly accessible human cell source, peripheral blood cells (PBCs), we derived a good manufacturing practice-compatible iPSC source, PBC-derived iPSCs (PBC-iPSCs) for this purpose. Through our original protocol that excludes CD34+ cell enrichment and spin embryoid body formation, high-purity functional and expandable NK cells were generated from PBC-iPSCs. Above all, most of these NK cells expressed no killer cell immunoglobulin-like receptors (KIRs), which renders them unrestricted by recipients' human leukocyte antigen genotypes. Hence, we have established a practical "from blood cell to stem cells and back with less (less KIRs)" strategy to generate abundant "universal" NK cells from PBC-iPSCs for a wide range of patients.
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