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:Ex Vivo IL-15-Stimulated NK Cells as Adoptive Cell Therapy in Haploidentical Transplantation for Pediatric Leukemia.
Ex Vivo IL-15-Stimulated NK Cells as Adoptive Cell Therapy in Haploidentical Transplantation for Pediatric Leukemia.
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一项I/II期临床试验在高危恶性肿瘤儿科患者中开展,旨在评估haplo-HSCT后输注NK细胞的安全性和有效性。患者接受来自KIR/HLA不匹配供者的同种反应性NK细胞或来自KIR/HLA匹配供者的IL-15刺激NK细胞,分为三个剂量递增队列。IL15-NK细胞输注产品表现出增强的活化受体表达和功能能力。在接受IL15-NK细胞的患者中,观察到NK细胞上NKG2D表达增加。一年随访显示,allo-NK和IL15-NK细胞组均出现免疫重建加速。IL15-NK受者表现出促炎细胞因子谱(IL-2、IL-4、IL-6、IFN-)。CD69表达升高与移植相关并发症风险较高相关。
A Phase I/II clinical trial was conducted in pediatric patients with high-risk malignancies to assess the safety and efficacy of NK cell infusion post-haplo-HSCT. Patients received either alloreactive NK cells from KIR/HLA-mismatched donors or IL-15-stimulated NK cells from KIR/HLA-matched donors, across three dose-escalating cohorts. The IL15-NK cell infusion product demonstrated enhanced activating receptor expression and functional capacity.
Increased NKG2D expression was observed in NK cells from patients receiving IL15-NK cells. One-year follow-up showed accelerated immune reconstitution in both the allo-NK and IL15-NK cell arms. IL15-NK recipients exhibited a pro-inflammatory cytokine profile (IL-2, IL-4, IL-6, IFN- ). Elevated CD69 expression was associated with a higher risk of transplant-related complications.
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