RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Clinical grade production of IL-15 stimulated NK cells for early infusion in adult AML patients undergoing haploidentical stem cell transplantation with post-transplant cyclophosphamide.
Clinical grade production of IL-15 stimulated NK cells for early infusion in adult AML patients undergoing haploidentical stem cell transplantation with post-transplant cyclophosphamide.
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我们的结果证明了在 AML 患者单倍体移植中,使用来自成年异基因供者的制备 NK IL15 细胞的安全性和可行性。
异基因造血干细胞移植是急性髓系白血病(AML)患者的首选治疗。对于需要及时移植但没有合适相合供者的患者,通常采用未操作的单倍体相合移植(Haplo-HSCT),但复发率仍较高,亟待改进。过继自然杀伤(NK)细胞免疫治疗可能有助于改善Haplo-HSCT,但迄今尚未建立最佳的细胞输注和制备方案。 研究设计与方法:本研究介绍一种快速、可重复的临床级单倍体相合供者NK细胞制备方案,采用两步免疫磁性去除与富集流程,并以IL-15刺激过夜。
研究共制备出8份具有活性和功能的NK细胞产品,并安全输注给5名接受未操作Haplo-HSCT的AML患者。 讨论:结果表明,在AML单倍体相合移植情境下,利用成年异基因供者制备IL-15刺激的NK细胞具有安全性和可行性。
Allogeneic stem cell transplantation is the treatment of choice for acute myeloid leukemia (AML) patients. Unmanipulated haploidentical transplantation (Haplo-HSCT) is commonly used for those AML patients who need a timely transplant and do not have a suitable matched donor, but relapse rates are still high, and improvements are needed. Adoptive immunotherapy using natural killer cells (NK cells) could be a promising tool to improved Haplo-HSCT but, to date, no optimal infusion and manufacturing protocols have been developed. STUDY DESIGN AND METHODS: In this study, we describe a quick and reproducible protocol for clinical-grade production of haploidentical donor NK cells using double immunomagnetic depletion and enrichment protocol and overnight IL-15 stimulation.
Thus, we have obtained 8 viable and functional NK cell products that have been safely infused to five AML patients undergoing unmanipulated Haplo-HSCT. DISCUSSION: Our results demonstrate the safety and feasibility of manufactured NK IL15 cells obtained from an adult allogeneic donor in the setting of haploidentical transplantation for AML patients.
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