肿瘤细胞治疗研究
英文原题：Manufacturing of primary CAR-NK cells in an automated system for the treatment of acute myeloid leukemia.
急性髓系白血病（AML）仍然是一种可怕的疾病，治疗选择有限。
急性髓系白血病（AML）仍然是一种治疗选择有限的可怕疾病。嵌合抗原受体（CAR）修饰的T细胞难以靶向AML，部分原因是缺乏真正AML独有的抗原以及该疾病的异质性。自然杀伤（NK）细胞对AML具有高度的内在杀伤能力，可能非常适合用于该疾病的治疗。然而，原代CAR-NK细胞的生成可能困难且耗时。因此，需要稳健的系统在GMP条件下生成大量CAR-NK细胞。在此，我们报道了使用CliniMACS Prodigy平台自动化生成大量靶向CD33的原代CAR-NK细胞。自动化生产的CD33-CAR-NK细胞在体外显示出与小规模生产的CD33-CAR-NK细胞相似的表型和细胞毒性，并且在细胞产品跨站点运输后，能够在OCI-AML2 NSG-SGM3异种移植小鼠模型中在体内强烈减少白血病负荷。该技术可能非常适合用于生成针对广泛靶点的原代CAR修饰NK细胞，并可能促进临床转化。
Acute myeloid leukemia (AML) still constitutes a dreadful disease with limited therapeutic options. Chimeric antigen receptor (CAR)-modified T cells struggle to target AML partly due to a lack of true AML-exclusive antigens and heterogeneity of the disease. Natural killer (NK) cells possess a high intrinsic killing capacity against AML and might be well suited for the treatment of this disease. However, the generation of primary CAR-NK cells can be difficult and time consuming. Therefore, robust systems for the generation of high numbers of CAR-NK cells under GMP conditions are required. Here we report on the automated generation of high numbers of primary CD33-targeting CAR-NK cells using the CliniMACS Prodigy platform. Automated-produced CD33-CAR-NK cells showed similar phenotype and cytotoxicity compared to small-scale-produced CD33-CAR-NK cells in vitro and were able to strongly reduce leukemic burden in an OCI-AML2 NSG-SGM3 xenograft mouse model in vivo following a cross-site shipment of the cell product. This technology might be well suited for the generation of primary CAR-modified NK cells for a broad range of targets and could facilitate clinical transition.
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