Investigating Natural-killer cell activity modulation in the context of allogeneic cell therapy

Document Type

Article

Publication Date

2026

JAX Location

NYSCF

Abstract

Natural-killer (NK) cells are part of our innate immune system and exhibit cytotoxic properties that allow them to kill infected cells without prior sensitization. Their activity is administered by a balance in opposing activating and inhibitory signals that restrain effector function against healthy cells and offer a promising platform for allogeneic cell therapy. In this project, we investigated how modulating inhibitory signaling of HLA-E and CD47 influences NK92 cell degranulation using two target systems: iPSC-derived pancreatic progenitor cells engineered to express varying levels of HLA-E, and K562 cancer lines expressing differential HLA-E levels across multiple effector-to-target (E:T) ratios. NK activity was measured using CD107a surface expression as a marker for degranulation. CD107 expression was significantly reduced against genetically modified iPSC target lines compared to wild type controls and decreased with increasing CD47 density, consistent with CD47’s inhibitory role in NK activity. Additionally, HLA-low K562 cells showed greater NK activity, most clearly in the highest 2:1 E:T ratio. These findings support our following aim to use the CRISPR Cas9 system to create an inducible system for a sustainable overexpression in NK cell lines and primary NK cells. Plasmids pAU003 and PB-TRE-dCas9-KRAB-MeCP2 were grown, purified, and underwent complete digestion evidenced by electrophoresis.

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