期刊论文详细信息
Molecular Therapy: Methods & Clinical Development
Superior Expansion and Cytotoxicity of Human Primary NK and CAR-NK Cells from Various Sources via Enriched Metabolic Pathways
Ting Liu1  Hsiang-chi Tseng1  Dongfang Liu1  Chen Liu1  Yan Yang1  Jie-Gen Jiang1  Saiaditya Badeti1  Minh Tuyet Ma1 
[1] Department of Pathology, Immunology and Laboratory Medicine, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA;
关键词: NK;    CAR;    expansion;    CAR-NK;    cytotoxicity;    CD19-CAR-NK;   
DOI  :  
来源: DOAJ
【 摘 要 】

Clinical success of chimeric antigen receptor (CAR) T cell immunotherapy requires the engineering of autologous T cells, which limits the broader implementation of CAR cell therapy. The development of allogeneic and universal cell products will significantly broaden their application and reduce costs. Allogeneic natural killer (NK) cells can be used for universal CAR immunotherapy. Here, we develop an alternative approach for the rapid expansion of primary NK and CAR-NK cells with superior expansion capability and in vivo 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.

【 授权许可】

Unknown   

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