Generation of âOff-the-Shelfâ Natural Killer Cells from Peripheral Blood Cell-Derived Induced Pluripotent Stem Cells

Summary: Current donor cell-dependent strategies can only produce limited âmade-to-orderâ therapeutic natural killer (NK) cells for limited patients. To provide unlimited âoff-the-shelfâ 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 âfrom blood cell to stem cells and back with less (less KIRs)â strategy to generate abundant âuniversalâ NK cells from PBC-iPSCs for a wide range of patients. : To provide unlimited âoff-the-shelfâ NK cells that serve many recipients, Zeng and colleagues demonstrate a manufacturing scheme to mass-produce NK cells from peripheral blood cell-derived iPSCs (PBC-iPSCs). Through their original protocol, high-purity functional NK cells are generated from PBC-iPSCs. Most of these NK cells express no killer cell immunoglobulin-like receptors, which renders them unrestricted by recipients' HLA genotypes. Keywords: induced pluripotent stem cells, peripheral blood cells, natural killer cells, killer cell immunoglobulin-like receptors, cell therapy, immunotherapy, cancer, cytotoxicit