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Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways

Yan YangDepartment of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USASaiaditya BadetiDepartment of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USAHsiang-chi TsengDepartment of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USAMinh TuyetDepartment of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USATing LiuDepartment of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USAJie JiangDepartment of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USAChen LiuDepartment of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USADongfang LiuCenter for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, 205 South Orange Avenue, Newark, NJ 07101, USA

2020en

ABI

Annotatsiya

cytotoxicity from various sources (including peripheral blood, cord blood, and tumor tissue). We apply a human B-lymphoblastoid cell-line 721.221 (hereinafter, 221)-based artificial feeder cell system with membrane-bound interleukin 21 (mIL-21) to propagate NK and CAR-NK cells. The expansion capability, purity, and cytotoxicity of NK cells expanded with 221-mIL-21 feeder cells are superior to that of conventional K562-mIL-21 feeder cells. RNA sequencing (RNA-seq) data show that 221-mIL-21 feeder cell-expanded NK cells display a less differentiated, non-exhausted, limited fratricidal, memory-like phenotype correlated with enriched metabolic pathways, which explains underlying mechanisms. Thus, "off-the-shelf" NK and CAR-NK cells with superior functionalities and expansion using a genetically modified 221-mIL-21 feeder cell expansion system will greatly support clinical use of NK immunotherapy.

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Identifikatorlar

DOI: 10.1016/j.omtm.2020.06.014

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