CAR-NK cells with dual targeting of PD-L1 and MICA/B in lung cancer tumor models.

ABSTRACT:

Background

Chimeric antigen receptor (CAR) engineered natural killer (NK) cells have shown their efficacy and superiority against cancer and possess the potential to become off-the-shelf immunotherapy products. Nonetheless, some challenges associated with CAR-NK cells still exist including inhibitory receptor engagement, antigen escape, and inadequate activation.

Methods

Given this, based on the concept of synthetic biology, we rationally designed a novel dual-targeted CAR (dtCAR), primarily comprising PD-L1 nanoantibody (PD-L1^Nb) and NKG2D as the ectodomain, transmembrane and cytoplasmic domains (CP) of CD28, and the CP of 4-1BB and CD3ζ. NK92 cells were engineered to express this third-generation of dtCAR. We then elucidated the role of dtCAR-modified NK92 cells

SUBMITTER: Zhi L 

PROVIDER: S-EPMC11853679 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature