Generation of "Off-the-Shelf" Natural Killer Cells from Peripheral Blood Cell-Derived Induced Pluripotent Stem Cells
- PMID: 29173894
- PMCID: PMC5785702
- DOI: 10.1016/j.stemcr.2017.10.020
Generation of "Off-the-Shelf" Natural Killer Cells from Peripheral Blood Cell-Derived Induced Pluripotent Stem Cells
Abstract
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.
Keywords: cancer; cell therapy; cytotoxicity; immunotherapy; induced pluripotent stem cells; killer cell immunoglobulin-like receptors; natural killer cells; peripheral blood cells.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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References
-
- Benson D.M., Jr., Cohen A.D., Jagannath S., Munshi N.C., Spitzer G., Hofmeister C.C., Efebera Y.A., Andre P., Zerbib R., Caligiuri M.A. A phase I trial of the anti-KIR antibody IPH2101 and lenalidomide in patients with relapsed/refractory multiple myeloma. Clin. Cancer Res. 2015;21:4055–4061. - PMC - PubMed
-
- Colucci F., Caligiuri M.A., Di Santo J.P. What does it take to make a natural killer? Nat. Rev. Immunol. 2003;3:413–425. - PubMed
-
- De Obaldia M.E., Bhandoola A. Transcriptional regulation of innate and adaptive lymphocyte lineages. Annu. Rev. Immunol. 2015;33:607–642. - PubMed
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