人源重编程 CD8 T 细胞的细胞治疗对 C57BL/6 小鼠 Lewis 肺癌转移具有抑制作用。
Cell Therapy with Human Reprogrammed CD8 T-Cells Has Antimetastatic Effects on Lewis Lung Carcinoma in C57BL/6 Mice.
机构信息
Laboratory of Regenerative Pharmacology, Goldberg ED Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Centre of the Russian Academy of Sciences, Lenin, 3, 634028 Tomsk, Russia.
Ministry of Health of the Russian Federation, Siberian State Medical University, Moskovski, 2, 634050 Tomsk, Russia.
出版信息
Int J Mol Sci. 2022 Dec 12;23(24):15780. doi: 10.3390/ijms232415780.
Using a model of Lewis lung carcinoma (LLC) in vitro and in vivo, we previously demonstrated increased antitumor activity in CD8 T-cells reprogrammed with an MEK inhibitor and PD-1 blocker. In this follow-up study, we carried out the reprogramming of human CD8 T-cells (hrT-cell) using the MEK inhibitor and PD-1 blocker and targeted LLC cells. The effects of hrT-cell therapy were studied in a mouse model of spontaneous metastasis of a solid LLC tumor. We found antimetastatic activity of hrT-cells, a decrease in the number of cancer cells and cancer stem cells in the lungs, and an increase in the number of T-cells in the blood (including effector T-cells). Thus, reprogramming of human CD8 T-cells with an MEK inhibitor and PD-1 blocker with targeted training by tumor target cells is a potential platform for developing a new approach to targeted lung cancer therapy.
先前，我们通过 Lewis 肺癌（LLC）的体外和体内模型，证实了经 MEK 抑制剂和 PD-1 阻断剂重编程的 CD8 T 细胞具有更强的抗肿瘤活性。在这项后续研究中，我们使用 MEK 抑制剂和 PD-1 阻断剂对人 CD8 T 细胞（hrT 细胞）进行了重编程，并靶向 LLC 细胞。我们在自发性 LLC 实体瘤转移的小鼠模型中研究了 hrT 细胞治疗的效果。我们发现 hrT 细胞具有抗转移活性，肺内癌细胞和癌症干细胞数量减少，血液中 T 细胞数量（包括效应 T 细胞）增加。因此，用 MEK 抑制剂和 PD-1 阻断剂对人 CD8 T 细胞进行重编程，并通过肿瘤靶细胞进行靶向训练，是开发针对肺癌治疗新方法的潜在平台。
Zotero 插件