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对于血液性恶性瘤的协同药物组合的ex vivo发现

Kamran A Ali¹, Reecha D Shah², Anukriti Dhar²

¹Notable Labs, 320 Hatch Dr, Foster City, CA, 94404, USA; Department of Biomedical Engineering, University of California, Irvine, 3120 Natural Sciences II, Irvine, CA, 92697, USA.

SLAS discovery : advancing life sciences R & D

|December 15, 2023

概括

一个新的平台,ComboFlow,使用患者白血病样本选药物组合,识别有效的治疗方法. 这种方法改善了针对急性骨髓性白血病 (AML) 和骨髓发育综合征的个性化医疗.

科学领域:

血液瘤学血液瘤学
药物发现和开发药物发现和开发
计算生物学计算生物学

背景情况:

组合疗法提高了急性髓性白血病 (AML) 治疗结果,但整体存活率仍然很差.
目前用于组合疗法的高通量查 (HTS) 方法依赖于具有有限临床相关性的细胞系.
开发个性化治疗需要先进的查策略,使用初级患者样本.

研究的目的:

开发一个新的HTS平台,ComboFlow,用于识别有效的组合疗法.
使用高度可翻译的ex vivo疾病模型,以大小有限的原发性白血病样本 (AML和骨髓质疏松综合征).
为了实现针对个性化癌症治疗的大规模药物组合景观的高效选.

主要方法:

组合Flow集成MiniFlow (微型流细胞计用于外体查),ComboPooler (组合药物组合的计算设计) 和AutoGater (用于自动流细胞计数据分析的机器学习).
在20个患者样本中选了3000多种药物组合,使用最小的细胞 (每样本600万).
验证了平台识别已知的协同作用药物组合和新型有效疗法的能力.

主要成果:

组合流成功地确定了博尔特佐米布和帕诺宾诺斯塔特的协同作用组合.
发现了一种新的达克提诺米辛和弗鲁达拉宾的协同作用组合,在AML样本的35%中有效.
这种新组合对正常的造血原体有有限的毒性,这表明了治疗潜力.

结论:

康博Flow提供了一个可访问的平台,用于在ex vivo模型中探索广泛的药物组合可能性.
该平台有助于发现更有效和个性化的血液恶性瘤组合疗法.
康博弗洛 (ComboFlow) 有望在癌症中推进个性化医疗,这种癌症可以通过体外模型来治疗.

关键词:

急性骨髓性白血病 (AML) 是一种急性骨髓性白血病.癌症癌症癌症癌症药物发现药物发现高通量选的高通量选精准医学是一门精准的医学.流动细胞计量是流动细胞计量的方法.

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