Targeted integration of EpCAM-specific CAR in human induced pluripotent stem cells and their differentiation into NK cells.

ABSTRACT:

Background

Redirection of natural killer (NK) cells with chimeric antigen receptors (CAR) is attractive in developing off-the-shelf CAR therapeutics for cancer treatment. However, the site-specific integration of a CAR gene into NK cells remains challenging.

Methods

In the present study, we genetically modified human induced pluripotent stem cells (iPSCs) with a zinc finger nuclease (ZFN) technology to introduce a cDNA encoding an anti-EpCAM CAR into the adeno-associated virus integration site 1, a "safe harbour" for transgene insertion into human genome, and next differentiated the modified iPSCs into CAR-expressing iNK cells.

Results

We detected the targeted integration in 4 out of 5 selected iPSC clones, 3 of which were biallelically modified. Southern blotting ana

SUBMITTER: Tang SY 

PROVIDER: S-EPMC8607711 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature