Purinergic targeting enhances immunotherapy of CD73⁺ solid tumors with piggyBac-engineered chimeric antigen receptor natural killer cells.

ABSTRACT:

Background

The anti-tumor immunity of natural killer (NK) cells can be paralyzed by the CD73-induced generation of immunosuppressive adenosine from precursor ATP within the hypoxic microenvironment of solid tumors. In an effort to redirect purinergic immunosuppression of NK cell anti-tumor function, we showed, for the first time, that immunometabolic combination treatment with NKG2D-engineered CAR-NK cells alongside blockade of CD73 ectonucleotidase activity can result in significant anti-tumor responses in vivo.

Methods

NK cells were engineered non-virally with NKG2D.CAR-presenting vectors based on the piggyBac transposon system with DAP10 and CD3ζ co-signaling domains. The anti-tumor immunity of NKG2D.CAR.NK cells in combination with CD73 targeting was evaluated against mu

SUBMITTER: Wang J 

PROVIDER: S-EPMC6278070 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature