研究动态
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在口腔癌、胰腺癌、胶质母细胞瘤、肝癌、黑色素瘤和卵巢癌的人源化骨髓肝和胸腺 (Hu-BLT) 小鼠模型中基于增强 NK 细胞的免疫疗法。

Supercharged NK Cell-Based Immuotherapy in Humanized Bone Marrow Liver and Thymus (Hu-BLT) Mice Model of Oral, Pancreatic, Glioblastoma, Hepatic, Melanoma and Ovarian Cancers.

发表日期:2023
作者: Kawaljit Kaur, Anahid Jewett
来源: Bone & Joint Journal

摘要:

在本文中,我们回顾了许多关于增压 NK (sNK) 细胞疗法在消除或治疗癌症方面的功效的体外和体内研究。我们使用 hu-BLT 小鼠,使用六种不同类型的口腔癌、胰腺癌、胶质母细胞瘤、黑色素瘤、肝癌和卵巢癌模型进行了研究。我们的体外研究表明,原代 NK 细胞优先靶向癌症干细胞样细胞 (CSC)/低分化肿瘤,而 sNK 细胞同时靶向 CSC/低分化和高分化肿瘤,显着高于原代活化 NK 细胞。我们对人源化 BLT 小鼠的体内研究表明,单独使用 sNK 细胞或与其他癌症治疗药物联合使用可预防肿瘤生长和转移。此外,sNK细胞能够增加骨髓、脾脏、牙龈、胰腺和外周血中免疫细胞的IFN-γ分泌和细胞毒功能。此外,在体外和体内研究中,sNK 细胞能够增强 CD8 T 细胞的扩增和功能。总体而言,我们的研究表明,单独使用 sNK 细胞或与其他癌症疗法联合使用,不仅可以有效消除侵袭性癌症,而且还能够增加 CD8 T 细胞的扩增和功能,以进一步靶向癌细胞,从而提供了一种成功的方法根除和治愈癌症。
In this paper, we review a number of in vitro and in vivo studies regarding the efficacy of supercharged NK (sNK) cell therapy in elimination or treatment of cancer. We have performed studies using six different types of cancer models of oral, pancreatic, glioblastoma, melanoma, hepatic and ovarian cancers using hu-BLT mice. Our in vitro studies demonstrated that primary NK cells preferentially target cancer stem-like cells (CSCs)/poorly differentiated tumors whereas sNK cells target both CSCs/poorly-differentiated and well-differentiated tumors significantly higher than primary activated NK cells. Our in vivo studies in humanized-BLT mice showed that sNK cells alone or in combination with other cancer therapeutics prevented tumor growth and metastasis. In addition, sNK cells were able to increase IFN-γ secretion and cytotoxic function by the immune cells in bone marrow, spleen, gingiva, pancreas and peripheral blood. Furthermore, sNK cells were able to increase the expansion and function of CD8+ T cells both in in vitro and in vivo studies. Overall, our studies demonstrated that sNK cells alone or in combination with other cancer therapeutics were not only effective against eliminating aggressive cancers, but were also able to increase the expansion and function of CD8+ T cells to further target cancer cells, providing a successful approach to eradicate and cure cancer.