TY  - JOUR
T1  - Optimization and Clinical-Scale Production of GMP-Grade NK Cells for Adoptive Cancer Immunotherapy
A1  - P. Davies
A1  - S. Johnson
A1  - R. Miller
JF  - Asian Journal of Current Research in Clinical Cancer
JO  - Asian J Curr Res Clin Cancer
SN  - 3062-4444
Y1  - 2022
VL  - 2
IS  - 1
DO  - 10.51847/0mz81D1ojH
SP  - 84
EP  - 100
N2  - Natural killer (NK) cells are a promising avenue for cancer immunotherapy, but efficient clinical-scale production remains challenging. Here, we present an optimized protocol for the activation and expansion of NK cells (NKAE) and its validation under clinical-grade conditions. NK cells were expanded from either total peripheral blood mononuclear cells (PBMCs) or CD45RA+ subsets using irradiated K562 feeder cells expressing IL15-41BBL or IL21-41BBL, with culture media including RPMI-1640, SCGM, NK MACS, and TexMACS. Expansion rate, purity, activation markers, cytotoxic function, and transcriptomic changes were evaluated. Clinical-grade NKAE cells were produced using the CliniMACS Prodigy system. NK MACS and TexMACS media provided superior NK cell purity and minimal T cell contamination. While NKAE generation from CD45RA+ cells was feasible, PBMCs offered higher cell yield and purity. The greatest expansion and purity were achieved with PBMCs stimulated by K562mbIL21-41BBL, though activation status and cytotoxicity were similar across all conditions. Transcriptomic profiling revealed marked differences between resting NK cells and NKAE cells expanded with either IL15- or IL21-expressing feeders. All clinical-grade NKAE preparations met regulatory quality criteria. Our findings demonstrate that GMP-compliant NK cells suitable for immunotherapy can be efficiently expanded using different starting cell populations and feeder strategies, supporting their use in clinical applications.
UR  - https://galaxypub.co/article/optimization-and-clinical-scale-production-of-gmp-grade-nk-cells-for-adoptive-cancer-immunotherapy-uhmxyvokxt3qsav
ER  -