| Literature DB >> 34525347 |
Karrune V Woan1, Hansol Kim1, Ryan Bjordahl2, Zachary B Davis1, Svetlana Gaidarova2, John Goulding2, Brian Hancock2, Sajid Mahmood2, Ramzey Abujarour2, Hongbo Wang1, Katie Tuininga1, Bin Zhang1, Cheng-Ying Wu1, Behiye Kodal1, Melissa Khaw1, Laura Bendzick1, Paul Rogers2, Moyar Qing Ge2, Greg Bonello2, Miguel Meza2, Martin Felices1, Janel Huffman2, Thomas Dailey2, Tom T Lee2, Bruce Walcheck3, Karl J Malmberg4, Bruce R Blazar5, Yenan T Bryceson6, Bahram Valamehr2, Jeffrey S Miller7, Frank Cichocki8.
Abstract
Select subsets of immune effector cells have the greatest propensity to mediate antitumor responses. However, procuring these subsets is challenging, and cell-based immunotherapy is hampered by limited effector-cell persistence and lack of on-demand availability. To address these limitations, we generated a triple-gene-edited induced pluripotent stem cell (iPSC). The clonal iPSC line was engineered to express a high affinity, non-cleavable version of the Fc receptor CD16a and a membrane-bound interleukin (IL)-15/IL-15R fusion protein. The third edit was a knockout of the ecto-enzyme CD38, which hydrolyzes NAD+. Natural killer (NK) cells derived from these uniformly engineered iPSCs, termed iADAPT, displayed metabolic features and gene expression profiles mirroring those of cytomegalovirus-induced adaptive NK cells. iADAPT NK cells persisted in vivo in the absence of exogenous cytokine and elicited superior antitumor activity. Our findings suggest that unique subsets of the immune system can be modeled through iPSC technology for effective treatment of patients with advanced cancer.Entities:
Keywords: NK cell; acute myeloid leukemia; adaptive; iPSC; immunotherapy; induced pluripotent stem cell; multiple myeloma; natural killer cell; off-the-shelf
Mesh：
Year: 2021 PMID： 34525347 PMCID： PMC8642276 DOI： 10.1016/j.stem.2021.08.013
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 25.269