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Review Article

血液系统恶性肿瘤的生物治疗：走向无化疗的时代

卷 26, 期 6, 2019

页: [1002 - 1018] 页: 17

弟呕挨: 10.2174/0929867324666171006144725

价格: $65

摘要

不到70年前，绝大多数血液系统恶性肿瘤是无法治愈的疾病，预后不良。第二次世界大战后开始的现代化疗药物的发展，由于DNA的结构及其在癌症生物学和肿瘤细胞分裂中的作用的发现而显着加速。从用单药抗代谢药物治疗的急性淋巴细胞白血病患儿中观察到的第一次暂时缓解至第一次通过多药物化疗方案实现的治疗方法非常短暂。然而，尽管取得了巨大成功，但常规遗传毒性细胞抑制剂具有固有的狭窄治疗指数和广泛的毒性，这在许多情况下限制了它们的临床应用。在20世纪的最后十年，对某些恶性肿瘤的生物学知识的增加导致了第一种分子靶向药物的构思和发展，这些药物被设计用于抑制参与癌细胞存活的特定药物分子。技术和基因工程的进步使得能够产生结构复杂的抗癌大分子，称为生物制品，包括治疗性单克隆抗体，抗体 - 药物偶联物和抗体片段。药物递送系统（DDS）的开发，其中常规药物附着于各种类型的载体，包括纳米颗粒，脂质体或可生物降解的聚合物，代表了开发新的抗癌剂的替代方法。尽管附着于DDS的药物的抗肿瘤活性没有根本不同，但与常规（未结合的）药物相比，改善的药代动力学特征，降低的毒副作用和显着增加的治疗指数导致其抗肿瘤效力增强。 2011年批准用于治疗癌症的第一种免疫检查点抑制剂开创了癌症免疫疗法的时代。到目前为止，检查点抑制剂，双特异性T细胞参与者，过继性T细胞方法和癌症疫苗已加入该平台，主要由重组细胞因子，治疗性单克隆抗体和免疫调节剂代表。在具体的临床适应症中，常规药物已经被包含多种免疫疗法和/或靶向药剂的多药剂，无化疗方案所取代。新免疫治疗方法的抗癌活性的非常独特的机制不仅要求新的应答标准，而且还可能在不久的将来改变某些类型的恶性血液病的基本治疗范例。

关键词: 血液系统恶性肿瘤，生物制品，单克隆抗体，免疫检查点抑制剂，抗体 - 药物偶联物（ADC），可生物降解的聚合物，免疫调节剂（IMiD），双特异性T细胞接合者（BiTE）。

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