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Blood：如何提高抗癌药物血脑屏障的穿透率？

2019-05-23 MedSci MedSci原创

NGR-hTNFR-CHOPPCNSL血管通透性
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原发性中枢神经系统淋巴瘤（PCNSL）患者采用以大剂量甲氨蝶呤为基础的化疗，需要住院治疗和广泛的专业知识来管理相关毒副作用。采用R-CHOP可克服这些困难，但相关药物的血脑屏障（BBB）穿透性较差。肿瘤坏死因子-a与NGR结合 (NGR- hTNF，可诱导内皮细胞通透性，提高抑制剂的肿瘤可及性。研究人员推测NGF-hTNF可打破BBB，进而提高抗癌药物的渗透性和R-CHOP用于复发性/难治性PCN

原发性中枢神经系统淋巴瘤（PCNSL）患者采用以大剂量甲氨蝶呤为基础的化疗，需要住院治疗和广泛的专业知识来管理相关毒副作用。采用R-CHOP可克服这些困难，但相关药物的血脑屏障（BBB）穿透性较差。肿瘤坏死因子-a与NGR结合 (NGR- hTNF，可诱导内皮细胞通透性，提高抑制剂的肿瘤可及性。

研究人员推测NGF-hTNF可打破BBB，进而提高抗癌药物的渗透性和R-CHOP用于复发性/难治性PCNSL患者的活性，并对此进行验证。

予以患者6个疗程的R-CHOP21治疗，在第1个R-CHOP21疗程前予以NGR-hTNF(0.8 ug/m2)处理。本试验包含两个阶段：探索阶段，探究NGF-hTNF对药物代谢动力学和血管通透性的影响，通过DCE-MRI和99mTc-DTPA-SPECT和肿瘤组织中CD13的表达来进行评估；扩展阶段：以ORR作为主要评估指标。

在第一阶段中，如果12个患者有4个或更多的患者获得缓解，则可继续进行该研究。现对探索阶段（12位受试者）的试验结果进行总结分析。

结果：所有病例的肿瘤血管上均有CD13表达。NGR-hTNF可选择性增加肿瘤区域和癌周组织的血管通透性，而且不影响药物的血浆/脑脊液浓度。NGR-hTNF/R-CHOP联合方案的耐受性良好：仅有两例SAE，4级副反应几乎全是血液学方面的，均在无需减少或中断治疗的情况下得以解决。

NGR-hTNF/R-CHOP疗效显著，9位患者获得缓解（75%；95% CI 51-99%），其中8位为完全缓解。

总而言之，NGR-hTNF/R-CHOP联合方案用于大剂量预处理的患者安全性好。NGR-hTNF可特异性的增强肿瘤组织和癌周组织的血管通透性，促进快速的获得缓解，并长时间维持。

原始出处：

Andrés J. M. Ferreri， et al. R-CHOP preceded by blood-brain barrier permeabilization with engineered tumor necrosis factor-α in primary CNS lymphoma. Blood 2019 ：blood.2019000633； doi： https：//doi.org/10.1182/blood.2019000633

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    2019-05-25 zhangying8788

    #血脑屏障#

    0

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    2019-05-25 一叶知秋

    #抗癌药物#

    0

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    2019-05-25 sunylz

    #抗癌药#

    0

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    2019-05-24 坚强007

    向挑战病魔的科研人员致敬！向挑战病魔的科研人员致敬！

    0

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    2019-05-24 深海的鱼

    学习学习学习

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    2019-05-23 329523732

    不错

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