Immunotherapy based on adoptive transfer of genetically engineered T- and NK-cells is an area of active ongoing research and has proven highly efficacious for patients with certain B-cell malignancies. Use of NK cells and NK cell lines as carriers of chimeric antigen receptors (CARs) appears particularly promising, as this opens an opportunity for moving the therapy from autologous to the allogeneic (universal) format. This “off-the-shelf” approach is thought to significantly reduce the price of the treatment and make it available to many more patients in need. Yet, the efficacy of CAR-NK cells in vivo presently remains low, and boosting the activity of CAR NK cells via stronger tumor homing, resistance to tumor microenvironment, as well as greater cytotoxicity may translate into improved patient outcomes. Here, we established a derivative of a human NK cell line YT overexpressing a positive regulator of cytotoxicity, VAV1. Activity of YT-VAV1 cells obtained was assayed in vitro against several cancer cell lines and primary patient-derived cancer cells. YT-VAV1 cells outperform parental YT cells in terms of cytotoxicity.

中文翻译：

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VAV1 过表达的 YT 细胞对恶性细胞显示出改善的细胞毒性

基于基因工程 T 细胞和 NK 细胞过继转移的免疫疗法是一个正在进行的积极研究领域，并已证明对某些 B 细胞恶性肿瘤患者非常有效。使用 NK 细胞和 NK 细胞系作为嵌合抗原受体 (CAR) 的载体似乎特别有希望，因为这为将治疗从自体转为同种异体（通用）形式提供了机会。这种“现成的”方法被认为可以显着降低治疗价格，并使更多有需要的患者可以使用。然而，CAR-NK 细胞在体内的功效目前仍然很低，通过更强的肿瘤归巢、对肿瘤微环境的抵抗力以及更大的细胞毒性来提高 CAR NK 细胞的活性可能会转化为改善患者的预后。在这里，我们建立了人类 NK 细胞系 YT 的衍生物，该细胞系过表达细胞毒性的正调节剂 VAV1。获得的 YT-VAV1 细胞的活性在体外针对几种癌细胞系和原代患者来源的癌细胞进行了测定。YT-VAV1 细胞在细胞毒性方面优于亲本 YT 细胞。