不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
HDAC6 选择性抑制剂 NN-429 在自然杀伤（NK）/T 细胞淋巴瘤中具有高效力和药物协同作用
英文原题：High Efficacy and Drug Synergy of HDAC6-Selective Inhibitor NN-429 in Natural Killer (NK)/T-Cell Lymphoma.
查看英文原题
High Efficacy and Drug Synergy of HDAC6-Selective Inhibitor NN-429 in Natural Killer (NK)/T-Cell Lymphoma.
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中文摘要
NK/T细胞淋巴瘤（NKTCL）和γδ T细胞非霍奇金淋巴瘤（γδ T-NHL）是高度侵袭性的淋巴瘤，缺乏合理设计的疗法，依赖于从其他血液系统恶性肿瘤中重新利用的化疗药物。组蛋白去乙酰化酶（HDAC）已成为包括T细胞淋巴瘤在内的多种恶性肿瘤的靶点。本研究通过第二代抑制剂NN-429，展示了HDAC6抑制在NKTCL和γδ T-NHL中的探索性发现。NN-429具有纳摩尔级的体外HDAC6效力以及对HDAC6的高体外和细胞内选择性，与老一代抑制剂相比，还表现出较长的驻留时间和改善的药代动力学特性。在对γδ T-NHL和NKTCL表现出独特的选择性细胞毒性后，NN-429在这些疾病模型中显示出与临床药物依托泊苷的协同关系，以及与多柔比星、阿糖胞苷和SNS-032的潜在协同作用，为联合治疗策略开辟了途径。
展开英文摘要原文
NK/T-cell lymphoma (NKTCL) and γδ T-cell non-Hodgkin lymphomas (γδ T-NHL) are highly aggressive lymphomas that lack rationally designed therapies and rely on repurposed chemotherapeutics from other hematological cancers. Histone deacetylases (HDACs) have been targeted in a range of malignancies, including T-cell lymphomas.
This study represents exploratory findings of HDAC6 inhibition in NKTCL and γδ T-NHL through a second-generation inhibitor NN-429. With nanomolar in vitro HDAC6 potency and high in vitro and in cellulo selectivity for HDAC6, NN-429 also exhibited long residence time and improved pharmacokinetic properties in contrast to older generation inhibitors.
Following unique selective cytotoxicity towards γδ T-NHL and NKTCL, NN-429 demonstrated a synergistic relationship with the clinical agent etoposide and potential synergies with doxorubicin, cytarabine, and SNS-032 in these disease models, opening an avenue for combination treatment strategies.
论文信息
- 作者
- Garcha HK、Nawar N、Sorger H、Erdogan F、Aung MMK、Sedighi A、Manaswiyoungkul P、Seo HS
- 单位
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, 3359 Mississauga Road, Mississauga, ON L5L 1C6, Canada.Canada
- 期刊
- Pharmaceuticals (Basel, Switzerland)2022 Oct 26
- 原文标识
- PubMed 36355493 · DOI 10.3390/ph15111321
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