Institute of Molecular and Cellular Biology, SB RAS, Novosibirsk, Russian Federation.
Federal Research Clinical Center FMBA of Russia, Moscow, Russian Federation.
Biotechnol Appl Biochem. 2021 Aug;68(4):849-855. doi: 10.1002/bab.2001. Epub 2020 Aug 21.
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.
基于过继转移基因工程 T 细胞和 NK 细胞的免疫疗法是一个活跃的研究领域，已被证明对某些 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) 的载体似乎特别有前途，因为这为将治疗从自体转移到同种异体 (通用) 格式开辟了机会。这种“现成的”方法被认为可以显著降低治疗费用，并使更多有需要的患者受益。然而，CAR-NK 细胞在体内的疗效目前仍然较低，通过更强的肿瘤归巢、对肿瘤微环境的抵抗以及更大的细胞毒性来增强 CAR-NK 细胞的活性可能会转化为改善患者的预后。在这里，我们建立了一个过表达细胞毒性正调节剂 VAV1 的人 NK 细胞系 YT 的衍生物。在体外，我们针对几种癌细胞系和原代患者来源的癌细胞检测了 YT-VAV1 细胞的活性。YT-VAV1 细胞在细胞毒性方面优于亲本 YT 细胞。
