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Ibrutinib

肿瘤

关键词肿瘤 药物 BTK抑制剂

词汇介绍

拓展阅读

解析

Ibrutinib

       n. 伊布替尼;伊布鲁替尼;依鲁替尼

       This study evaluated the safety and efficacy of ibrutinib combined with rituximab (R) and bendamustine. 该项研究评估了伊布替尼联合利妥昔单抗以及苯达莫司汀治疗的安全性和有效性。

概述

伊布替尼是一种小分子布鲁顿酪氨酸激酶(BTK)抑制剂,能够与BTK活性中心的半胱氨酸残基共价结合,从而抑制B细胞的活动,对B细胞淋巴瘤疗效显著,尤其是对于难控制易复发的多种晚期淋巴瘤患者。与传统的治疗方法相比,伊布替尼表现出良好的优势,如其毒副作用少、活性强、选择性高。从而抑制其活性。伊布替尼是全球第一个上市的BTK抑制剂,由强生和Pharmacyclics合作开发,最早是于2013/11/13获得FDA批准上市,上市之后销售额突飞猛进,由此也引起了AbbVie的巨大兴趣。AbbVie于20

Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators复制标题

甘露糖化纳米抗体预防接种免疫抑制微环境的抑制使黑色素瘤对免疫检查点调节剂敏感

发表时间:2019-08-05

影响因子:33.4

作者: João Conniot

期刊:Nat Nanotechnol

A low response rate, acquired resistance and severe side effects have limited the clinical outcomes of immune checkpoint therapy. Here, we show that combining cancer nanovaccines with an anti-PD-1 antibody (αPD-1) for immunosuppression blockade and an anti-OX40 antibody (αOX40) for effector T-cell stimulation, expansion and survival can potentiate the efficacy of melanoma therapy. Prophylactic and therapeutic combination regimens of dendritic cell-targeted mannosylated nanovaccines with αPD-1/αOX40 demonstrate a synergism that stimulates T-cell infiltration into tumours at early treatment stages. However, this treatment at the therapeutic regimen does not result in an enhanced inhibition of tumour growth compared to αPD-1/αOX40 alone and is accompanied by an increased infiltration of myeloid-derived suppressor cells in tumours. Combining the double therapy with ibrutinib, a myeloid-derived suppressor cell inhibitor, leads to a remarkable tumour remission and prolonged survival in melanoma-bearing mice. The synergy between the mannosylated nanovaccines, ibrutinib and αPD-1/αOX40 provides essential insights to devise alternative regimens to improve the efficacy of immune checkpoint modulators in solid tumours by regulating the endogenous immune response.

译文

低反应率,获得性耐药和严重的副作用限制了免疫检查点治疗的临床结果。在这里,我们显示癌症纳米线虫与抗PD-1抗体(αPD-1)结合用于免疫抑制阻断和抗OX40抗体(αOX40)用于效应T细胞刺激,扩增和存活可以增强黑素瘤治疗的功效。树突细胞靶向甘露糖化纳米线虫与αPD-1 /αOX40的预防和治疗组合方案显示出在早期治疗阶段刺激T细胞浸润到肿瘤中的协同作用。然而,与单独的αPD-1 /αOX40相比,在治疗方案中的这种治疗不会导致肿瘤生长的抑制增强,并且伴随着肿瘤中髓源性抑制细胞的浸润增加。将双重疗法与源自骨髓的抑制细胞抑制剂依鲁替尼相结合,可以显着降低黑色素瘤小鼠的肿瘤缓解率和延长生存期。甘露糖基化纳米线虫,依鲁替尼和αPD-1 /αOX40之间的协同作用提供了基本的见解,以设计替代方案,通过调节内源性免疫应答来改善免疫检查点调节剂在实体瘤中的功效。