肿瘤细胞治疗研究
英文原题：Efficient, fratricide free non-viral engineering of CD70-targeted CAR NK cells for hematologic and solid tumor immunotherapy.
我们的发现展示了非病毒转座子介导的细胞工程联合 CRISPR-Cas9 敲除的新应用，可生产出用于针对多种癌症的 ACT 的临床可规模化产品。
自然杀伤（NK）细胞是先天免疫系统的组成部分，与T细胞相比，在过继细胞治疗（ACT）中可能具有安全性优势。然而，NK细胞缺乏清除肿瘤所需的效力和持久性。我们报告了一种高效且经济的非病毒方法，利用高活性TcBuster DNA转座子系统工程化构建靶向CD70的CAR NK细胞，同时通过CRISPR-Cas9敲除CD70以防止同类相残。经此方式工程化的CD70 CAR NK细胞，在体外和体内杀伤急性髓系白血病（AML）细胞及肾细胞癌（RCC）细胞的效能均有所提高。在转座子盒中加入可溶性IL-15细胞因子支持模块，进一步改善了其体内存活和扩增。我们的研究展示了一种新的非病毒转座子细胞工程与CRISPR-Cas9敲除相结合的应用，可制备具有临床规模化潜力、用于多种癌症ACT治疗的产品。
Natural killer (NK) cells are a component of the innate immune system with potential safety advantages over T cells for adoptive cell therapy (ACT). However, NK cells lack the potency and persistence needed for tumor clearance. Here, we report an efficient and cost-effective non-viral method for engineering CD70 targeted CAR NK cells using a hyperactive TcBuster DNA transposon system while simultaneously knocking out CD70 via CRISPR-Cas9 to prevent fratricide. CD70 CAR NK cells engineered in this manner display improved efficacy in killing acute myeloid lymphoma (AML) cells and renal cell carcinoma (RCC) cells in vitro and in vivo . Incorporating soluble IL-15 cytokine armoring into the transposon cassette further improves survival and expansion in vivo . Our findings demonstrate a novel application of non-viral transposon-based cell engineering combined with CRISPR-Cas9 knockout to produce a clinically scalable product for ACT against multiple cancer types.
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