High-affinity CD16 integration into a CRISPR/Cas9-edited CD38 locus augments CD38-directed antitumor activity of primary human natural killer cells.

ABSTRACT:

Background

Adoptive transfer of natural killer (NK) cells with augmented antibody-dependent cellular cytotoxicity (ADCC) capabilities and resistance to CD38 targeting has the potential to enhance the clinical anti-myeloma activity of daratumumab (DARA). Therefore, we sought to develop an efficient CRISPR/Cas9-based gene editing platform to disrupt CD38 expression (CD38 knockout (KO)) in ex vivo expanded NK cells and simultaneously arm CD38^KO NK cells with a high-affinity CD16 (CD16-158V) receptor.

Methods

CD38^KO human NK cells were generated using Cas9 ribonucleoprotein complexes. The platform was expanded by incorporating messenger RNA (mRNA) transfection of CD38^KO NK cells and targeted gene insertion at the CD38 locus to mediate gene

SUBMITTER: Clara JA 

PROVIDER: S-EPMC8830298 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature