Cell Therapy, Stem Cells and Tissues Group, Basque Centre for Blood Transfusion and Human Tissues, Galdakao, Spain.
Biocruces Bizkaia Health Research Institute, Barkaldo, Spain.
Sci Rep. 2019 Dec 10;9(1):18729. doi: 10.1038/s41598-019-55239-y.
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, CAR T 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.
在血液系统恶性肿瘤中,急性淋巴细胞白血病(ALL)和慢性淋巴细胞白血病(CLL)分别是儿童和老年人中最常见的白血病。一些患者对化疗治疗没有反应,需要辅以免疫治疗,如嵌合抗原受体(CAR)治疗,这是针对这些癌症和 B 细胞淋巴瘤的最新且最有效的治疗方法之一。尽管完全缓解的结果很有希望,但 CAR T 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 CAR 治疗免疫细胞来源,它可能在有效靶向恶性细胞的同时预防这些副作用。来自不同来源的 NK 细胞是 CAR 治疗的一种很有前途的载体,因为它们在同种异体治疗中不会引起移植物抗宿主病(GvHD),并且无需预先致敏即可迅速攻击癌细胞。我们研究了成人外周血(AB)和脐带血(CB)来源的 NK 细胞对不同靶细胞的疗效,以确定 CAR 治疗的最佳来源。AB CAR-NK 细胞在杀伤表达 CD19 的靶细胞方面略胜一筹,而 CB NK 细胞更容易被刺激,并且其数量在供体间更为稳定。我们得出结论,两种来源的 CAR-NK 细胞都有其优势,可作为 CAR 治疗的替代和更安全的候选物。