TP53 缺失通过上调 NF-κB-IFN-β-MHC-Ia 信号促进骨肉瘤对 NK 细胞的抵抗
TP53 Loss Elevates NF-κB-IFN-β-MHC-Ia Signaling to Promote NK Cell Resistance in Osteosarcoma.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Engineered Mesenchymal Stem Cells as Treatment for Cancers: Opportunities, Clinical Applications and Challenges.
Engineered Mesenchymal Stem Cells as Treatment for Cancers: Opportunities, Clinical Applications and Challenges.
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传统化疗药物靶向性不足且不够特异,常导致治疗耐药和癌症复发。过去数十年对间充质干细胞(MSC)生物学的发现,为改进癌症治疗提供了新的潜在途径。研究者利用 MSC 的多向分化、再生和免疫抑制特性,以及其对炎症、缺氧和恶性病灶的趋向性,将其用于多种治疗应用。尽管 MSC 疗法总体上已显示安全,但单独使用 MSC 时疗效仍有限。然而,通过基因工程改造,研究者已证明可赋予 MSC 专门的递送功能,提高其癌症治疗效力。通过病毒或非病毒基因修饰,可使 MSC 过表达治疗性蛋白,从而增强其固有特性。尽管如此,仍需优化这些工程策略,以提高治疗效力和靶向效果,同时尽量减少 MSC 功能损失。本综述重点介绍 MSC 工程化的前沿方法,讨论其前景及临床转化困难,并对如何充分发挥其治疗潜力提出未来展望。
The insufficient and unspecific target of classical chemotherapies often leads to therapy resistance and cancer recurrence. Over the past decades, discoveries about mesenchymal stem cell (MSC) biology have provided new potential approaches to improve cancer therapy.
Researchers have utilised the multipotent, regenerative and immunosuppressive qualities of MSCs and tropisms towards inflammatory, hypoxic and malignant sites in various therapeutic applications. Although MSC-based therapies have generally been demonstrated safe, their effectiveness remains limited when these cells are used alone.
However, through genetic engineering, researchers have proven that MSCs can be modified to have specialised delivery roles to increase their therapeutic efficacy in cancer treatment. They can be made to overexpress therapeutic proteins through viral or non-viral genetic modification, which enhances their innate properties.
Nevertheless, these engineering strategies must be optimised to increase therapeutic efficacy and targeting effectiveness while minimising any loss of MSC function. This review underscores the cutting-edge methods for engineering MSCs, discusses their promise and the difficulties in translating them into clinical settings, and offers some prospective suggestions for the future on achieving their full therapeutic potential.
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