Unknown

Dataset Information

0

Human iPSC-Derived Natural Killer Cells Engineered with Chimeric Antigen Receptors Enhance Anti-tumor Activity.


ABSTRACT: Chimeric antigen receptors (CARs) significantly enhance the anti-tumor activity of immune effector cells. Although most studies have evaluated CAR expression in T cells, here we evaluate different CAR constructs that improve natural killer (NK) cell-mediated killing. We identified a CAR containing the transmembrane domain of NKG2D, the 2B4 co-stimulatory domain, and the CD3? signaling domain to mediate strong antigen-specific NK cell signaling. NK cells derived from human iPSCs that express this CAR (NK-CAR-iPSC-NK cells) have a typical NK cell phenotype and demonstrate improved anti-tumor activity compared with T-CAR-expressing iPSC-derived NK cells (T-CAR-iPSC-NK cells) and non-CAR-expressing cells. In an ovarian cancer xenograft model, NK-CAR-iPSC-NK cells significantly inhibited tumor growth and prolonged survival compared with PB-NK cells, iPSC-NK cells, or T-CAR-iPSC-NK cells. Additionally, NK-CAR-iPSC-NK cells demonstrate in vivo activity similar to that of T-CAR-expressing T cells, although with less toxicity. These NK-CAR-iPSC-NK cells now provide standardized, targeted "off-the-shelf" lymphocytes for anti-cancer immunotherapy.

SUBMITTER: Li Y 

PROVIDER: S-EPMC6084450 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC5604792 | biostudies-literature
| S-EPMC7720606 | biostudies-literature
| S-EPMC4412125 | biostudies-literature
| S-EPMC5768663 | biostudies-literature
| S-EPMC6524286 | biostudies-literature
| S-EPMC3967004 | biostudies-literature
| S-EPMC6278070 | biostudies-literature
| S-EPMC8410173 | biostudies-literature
| S-EPMC5835122 | biostudies-literature
| S-EPMC8524382 | biostudies-literature