肿瘤细胞治疗研究
英文原题：CAR NK cell production from human cord blood NK progenitor cells is enhanced by stimulation of the IL-15 receptor.
这些结果提示，表达 4-1BBL、mbIL-21 和 mbIL-15 的 K562 饲养层细胞可提高由脐带血（CB）细胞制备 CAR-NK 细胞的产量，同时保持其细胞毒性潜力。
脐带血（CB）来源嵌合抗原受体（CAR）自然杀伤（NK）细胞已显示出显著抗肿瘤疗效。我们近期报告，CB来源CAR-NK细胞主要来自脐带血中的CD7+ CD56− CD34− HLA-DR− Lin− NK细胞前体。本研究显示，刺激这些NK前体的白细胞介素15（IL-15）受体可增强脐带血细胞产生CAR-NK细胞的能力。在CB CD56− CD34− HLA-DR− Lin−细胞中，IL-15受体仅表达于CD7+ NK细胞前体。使用同时表达4-1BB配体、膜结合型（mb）IL-21和mbIL-15的K562饲养细胞，可显著增加纯化NK前体或去除T细胞后的脐带血细胞生成成熟NK细胞的数量。使用表达mbIL-15的K562饲养细胞制备的CAR-NK细胞，其体内外抗肿瘤作用与使用不表达mbIL-15的饲养细胞制备的CAR-NK细胞相当。这些结果提示，同时表达4-1BBL、mbIL-21和mbIL-15的K562饲养细胞可提高脐带血细胞的CAR-NK产量，同时保留细胞毒潜力。无论是否进行CAR转导，该方法也可用于扩增脐带血NK细胞，以开展各类过继NK细胞治疗。
Cord blood (CB)-derived chimeric antigen receptor (CAR) natural killer (NK) cells have demonstrated significant antitumor efficacy. We recently reported that CB-derived CAR NK cells predominantly originate from CD7 + CD56 - CD34 - HLA-DR - Lin - NK cell precursors in CB. Here, we demonstrate that stimulating the interleukin (IL)-15 receptor on these NK precursors enhances the production of CAR NK cells from CB cells. In CB CD56 - CD34 - HLA-DR - Lin - cells, the IL-15 receptor was exclusively expressed on CD7 + NK cell precursors. Using K562 feeder cells that express not only 4-1BB ligand and membrane-bound (mb) IL-21 but also mbIL-15 significantly increased the production of mature NK cells from the purified NK cell precursors or T cell-depleted CB cells. The in vitro and in vivo antitumor effects of CAR NK cells generated using K562 feeder cells that express mbIL-15 were comparable to those of CAR NK cells produced using K562 feeder cells that do not express mbIL-15. These results suggest that K562 feeder cells expressing 4-1BBL, mbIL-21, and mbIL-15 can increase the production of CAR NK cells from CB cells while maintaining their cytotoxic potential. This method could also be useful for expanding NK cells from CB for any type of adoptive NK cell therapy with or without CAR transduction.
MEMBER ACCOUNT
登录成功会直接打开下一页。
