磁纳米颗粒附着在 NK 细胞表面用于过继转移治疗中的肿瘤靶向,不会影响细胞效应功能。
Magnetic Nanoparticles Attached to the NK Cell Surface for Tumor Targeting in Adoptive Transfer Therapies Does Not Affect Cellular Effector Functions.
机构信息
Department of Immunology and Oncology, and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)-CSIC, Madrid, Spain.
出版信息
Front Immunol. 2019 Aug 30;10:2073. doi: 10.3389/fimmu.2019.02073. eCollection 2019.
Adoptive cell transfer therapy is currently one of the most promising approaches for cancer treatment. This therapy has some limitations, however, such as the dispersion of -administered cells, causing only a small proportion to reach the tumor. Nanotechnological approaches could offer a solution for this drawback, as they can increase cell retention and accumulation in a region of interest. In particular, strategies employing magnetic nanoparticles (MNPs) to improve targeting of adoptively transferred T or NK cells have been explored in mice. magnetic retention is reported using the human NK cell line NK-92MI transfected with MNPs. Primary NK cells are nonetheless highly resistant to transfection, and thus we explore in here the possibility of attaching the MNPs to the NK cell surface to overcome this issue, and examine whether this association would affect NK effector functions. We assessed the attachment of MNPs coated with different polymers to the NK cell surface, and found that APS-MNP attached more efficiently to the NK-92MI cell surface. In association with MNPs, these cells preserved their main functions, exhibiting a continued capacity to degranulate, conjugate with and lyse target cells, produce IFN-γ, and respond to chemotactic signals. MNP-loaded NK-92MI cells were also retained in an capillary flow system by applying an EMF. A similar analysis was carried out in primary NK cells, isolated from mice, and expanded . These primary murine NK cells also maintained their functionality intact after MNP treatment and were successfully retained . This work therefore provides further support for using MNPs in combination with EMFs to favor specific retention of functional NK cells in a region of interest, which may prove beneficial to adoptive cell-therapy protocols.
过继细胞转移疗法是目前癌症治疗最有前途的方法之一。然而,这种疗法存在一些局限性,例如-给予的细胞分散,只有一小部分到达肿瘤。纳米技术方法可以解决这个缺点,因为它们可以增加细胞在感兴趣区域的保留和积累。特别是,使用磁性纳米粒子 (MNP) 来提高过继转移的 T 或 NK 细胞靶向性的策略已经在小鼠中进行了探索。已经报道了使用转染 MNP 的人 NK 细胞系 NK-92MI 进行磁性保留。然而,原代 NK 细胞对转染具有高度抗性,因此我们在这里探索了将 MNP 附着到 NK 细胞表面以克服这个问题的可能性,并研究这种结合是否会影响 NK 效应功能。我们评估了不同聚合物涂覆的 MNP 附着到 NK 细胞表面的情况,发现 APS-MNP 更有效地附着到 NK-92MI 细胞表面。与 MNP 结合后,这些细胞保持了其主要功能,继续具有脱颗粒、与靶细胞结合和裂解、产生 IFN-γ以及对趋化信号做出反应的能力。在施加 EMF 的情况下,负载 MNP 的 NK-92MI 细胞也可以在毛细血管流动系统中保留。对从小鼠中分离并扩增的原代 NK 细胞进行了类似的分析。这些原代小鼠 NK 细胞在 MNP 处理后仍保持其功能完整,并成功保留。因此,这项工作进一步支持将 MNP 与 EMF 结合使用,以有利于在感兴趣的区域中特异性保留功能性 NK 细胞,这可能对过继细胞治疗方案有益。