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:Adoptive NK cell therapy in AML: progress and challenges.
Adoptive NK cell therapy in AML: progress and challenges.
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使用自然杀伤(NK)细胞的过继细胞疗法(ACT)已成为治疗急性髓系白血病(AML)的一种有前景的治疗策略,可应对化疗耐药和高复发率等挑战。多年来,临床试验和研究探索了多种NK细胞来源,包括体外扩增的NK细胞系、CAR-NK细胞、外周血来源的NK细胞以及脐带血来源的NK细胞。这些疗法已展现出不同程度的治疗疗效,从短暂的抗白血病活性到在特定患者群体中实现持续缓解。毒性特征总体显示出良好的安全性结局,严重不良事件如细胞因子释放综合征(CRS)或移植物抗宿主病(GVHD)的发生率极低。
然而,持续存在的挑战仍然包括NK细胞持久性有限、复发以及患者反应的异质性。本综述对过去15年开展的临床试验、临床研究和病例报告中提供的临床结局和毒性特征进行了全面分析,以评判使用NK细胞进行AML的ACT的疗效、安全性和适用性。本综述强调了基于NK细胞的疗法对AML的巨大潜力,同时探讨了为提高其疗效和安全性必须克服的技术和生物学挑战。
Adoptive cell therapy (ACT) using natural killer (NK) cells has emerged as a promising therapeutic strategy for acute myeloid leukemia (AML), addressing challenges such as chemotherapy resistance and high relapse rates. Over the years, clinical trials and studies have explored various sources of NK cells, including ex vivo expanded NK cell lines, CAR-NK cells, peripheral blood-derived NK cells, and umbilical cord blood-derived NK cells.
These therapies have demonstrated varying degrees of therapeutic efficacy, ranging from transient anti-leukemia activity to sustained remission in select patient groups. Toxicity profiles have generally shown favorable safety outcomes, with minimal incidence of severe adverse effects such as cytokine release syndrome (CRS) or graft-versus-host disease (GVHD).
However, persistent challenges remain, including limited NK cell persistence, relapse, and heterogeneity in patient responses. This review provides a comprehensive analysis of clinical outcomes and toxicity profiles provided from clinical trials, clinical studies and case reports conducted in the last 15 years to judge on the efficacy, safety and applicability of using NK cells for ACT of AML.
Our review highlights the significant potential of NK cell-based therapies for AML, while addressing the technical and biological challenges that must be overcome to enhance their efficacy and safety.
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