Past, Present, and Future of Rituximab-The World's First Oncology Monoclonal Antibody Therapy.
Past, Present, and Future of Rituximab-The World's First Oncology Monoclonal Antibody Therapy.
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Rituximab的过去，现在和未来 - 世界上第一种肿瘤学单克隆抗体疗法。
DOI：
10.3389/fonc.2018.00163
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发表时间：
2018
影响因子：
4.7
通讯作者：
Richards KL
中科院分区：
文献类型：
--
作者：
Pierpont TM;Limper CB;Richards KL
利妥昔单抗是一种嵌合小鼠/人单克隆抗体（mAb）治疗，具有与CD 20的结合特异性。它是第一个被批准用于肿瘤患者的治疗性抗体，并且是近十年来最畅销的肿瘤药物，2016年的销售额达到85.8亿美元。自1997年首次批准以来，它改善了所有B细胞恶性肿瘤的结局，包括弥漫性大B细胞淋巴瘤，滤泡性淋巴瘤和慢性淋巴细胞白血病。尽管广泛使用，但大多数机制数据都是从体外研究中收集的，而各种反应机制在人体中的作用在很大程度上仍然不确定。Fc γ受体和补体蛋白基因多态性已被认为是利妥昔单抗差异反应的潜在预测因子，但尚未显示出足以影响临床决策的影响力。与目前开发的大多数靶向治疗不同，除了降低肿瘤负荷外，还没有发现指示靶向接合/肿瘤反应的已知生物标志物。由于缺乏CD 20本身以外的伴随生物标志物，因此难以预测哪些患者会对任何给定的抗CD 20抗体产生应答。在过去的十年中，已经批准了两种新的抗CD 20抗体：奥法木单抗，其结合CD 20的不同表位，和obinutuzumab，一种衍生自利妥昔单抗的mAb，其对Fc部分及其糖基化进行了修饰。两者都是完全人源化的，并且具有与利妥昔单抗不同的生物活性。除了这些新的抗CD 20抗体外，靶向淋巴瘤治疗的另一个即将发生的变化是随着利妥昔单抗专利到期而出现的大量生物仿制药。虽然利妥昔单抗本身的广泛使用可能会继续，但其生物仿制药将增加全球对该疗法的使用。本文综述了利妥昔单抗反应的机制和潜在生物标志物，以及其生物仿制药和新的CD 20结合mAb治疗的研究。增加评估利妥昔单抗在个体患者中的有效性的能力，沿着替代抗CD 20抗体的可用性，可能会导致我们未来如何使用CD 20抗体的巨大变化。
Rituximab is a chimeric mouse/human monoclonal antibody (mAb) therapy with binding specificity to CD20. It was the first therapeutic antibody approved for oncology patients and was the top-selling oncology drug for nearly a decade with sales reaching $8.58 billion in 2016. Since its initial approval in 1997, it has improved outcomes in all B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia. Despite widespread use, most mechanistic data have been gathered from in vitro studies while the roles of the various response mechanisms in humans are still largely undetermined. Polymorphisms in Fc gamma receptor and complement protein genes have been implicated as potential predictors of differential response to rituximab, but have not yet shown sufficient influence to impact clinical decisions. Unlike most targeted therapies developed today, no known biomarkers to indicate target engagement/tumor response have been identified, aside from reduced tumor burden. The lack of companion biomarkers beyond CD20 itself has made it difficult to predict which patients will respond to any given anti-CD20 antibody. In the past decade, two new anti-CD20 antibodies have been approved: ofatumumab, which binds a distinct epitope of CD20, and obinutuzumab, a mAb derived from rituximab with modifications to the Fc portion and to its glycosylation. Both are fully humanized and have biological activity that is distinct from that of rituximab. In addition to these new anti-CD20 antibodies, another imminent change in targeted lymphoma treatment is the multitude of biosimilars that are becoming available as rituximab’s patent expires. While the widespread use of rituximab itself will likely continue, its biosimilars will increase global access to the therapy. This review discusses current research into mechanisms and potential biomarkers of rituximab response, as well as its biosimilars and the newer CD20 binding mAb therapies. Increased ability to assess the effectiveness of rituximab in an individual patient, along with the availability of alternative anti-CD20 antibodies will likely lead to dramatic changes in how we use CD20 antibodies going forward.
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影响因子：
6.5
作者：
Awasthi, Aradhana;Ayello, Janet;Cairo, Mitchell S.
通讯作者：
Cairo, Mitchell S.
影响因子：
1.8
作者：
Amin AD;Peters TL;Li L;Rajan SS;Choudhari R;Puvvada SD;Schatz JH
通讯作者：
Schatz JH
影响因子：
20.3
作者：
Alduaij, Waleed;Illidge, Tim M.
通讯作者：
Illidge, Tim M.
基于曲妥珠单抗的HER2阳性乳腺癌治疗：抗体依赖性细胞毒性机制？
影响因子：
8.8
作者：
Arnould, L;Gelly, M;Penault-Llorca, F;Benoit, L;Bonnetain, F;Migeon, C;Cabaret, V;Fermeaux, V;Bertheau, P;Garnier, J;Jeannin, JF;Coudert, B
通讯作者：
Coudert, B
影响因子：
51.1
作者：
Ardeshna, Kirit M.;Qian, Wendi;Linch, David C.
通讯作者：
Linch, David C.