Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells
Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells
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DOI：
10.1038/s41598-019-55239-y
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发表时间：
2019-12-10
影响因子：
4.6
通讯作者：
Eguizabal, C.
中科院分区：
文献类型：
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作者：
Herrera, L.;Santos, S.;Eguizabal, C.
在血液系统肿瘤中，急性淋巴细胞性白血病(ALL)和慢性淋巴细胞性白血病(CLL)分别是儿童和老年人最常见的白血病。一些患者对化疗没有反应，有必要以基于免疫治疗的治疗为补充，如嵌合抗原受体(CAR)治疗，这是针对这些癌症和B细胞淋巴瘤的最新和更有效的治疗方法之一。尽管完全缓解的结果很有希望，CART细胞治疗仍然存在一些风险，包括细胞因子释放综合征(CRS)和神经毒性。我们提出了一种不同的免疫细胞来源用于CAR治疗，该来源可能在有效靶向恶性细胞的同时防止这些副作用。来自不同来源的NK细胞是CAR治疗的一种有前途的载体，因为它们在同种异体治疗中不会引起移植物抗宿主病(GvHD)，而且它们可以在没有事先致敏的情况下迅速攻击癌细胞。为了确定CAR治疗的最佳来源，我们研究了成人外周血(AB)和脐带血(CB)中的NK细胞对不同靶细胞的杀伤作用。ABCAR-NK细胞对CD19呈递靶细胞的杀伤能力稍强，而CB-NK细胞更易被激发，其数量在不同供者之间较为稳定。我们得出结论，这两种来源的CAR-NK细胞都有各自的优势，可以作为CAR治疗的替代和更安全的候选细胞。
Among hematological cancers, Acute Lymphoblastic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL) are the most common leukemia in children and elderly people respectively. Some patients do not respond to chemotherapy treatments and it is necessary to complement it with immunotherapy-based treatments such as chimeric antigen receptor (CAR) therapy, which is one of the newest and more effective treatments against these cancers and B-cell lymphoma. Although complete remission results are promising, CART cell therapy presents still some risks for the patients, including cytokine release syndrome (CRS) and neurotoxicity. We proposed a different immune cell source for CAR therapy that might prevent these side effects while efficiently targeting malignant cells. NK cells from different sources are a promising vehicle for CAR therapy, as they do not cause graft versus host disease (GvHD) in allogenic therapies and they are prompt to attack cancer cells without prior sensitization. We studied the efficacy of NK cells from adult peripheral blood (AB) and umbilical cord blood (CB) against different target cells in order to determine the best source for CAR therapy. AB CAR-NK cells are slightly better at killing CD19 presenting target cells and CB NK cells are easier to stimulate and they have more stable number from donor to donor. We conclude that CAR-NK cells from both sources have their advantages to be an alternative and safer candidate for CAR therapy.