New antibody approaches to lymphoma therapy.
New antibody approaches to lymphoma therapy.
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DOI：
10.1186/s13045-014-0058-4
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发表时间：
2014-09-09
影响因子：
28.5
通讯作者：
Barta SK
中科院分区：
文献类型：
--
作者：
Suresh T;Lee LX;Joshi J;Barta SK
CD20导向的单抗利妥昔单抗开创了淋巴瘤治疗的新纪元。从那时起，淋巴瘤表面的其他表位被确定为单抗(MAb)的潜在靶点。虽然大多数单抗主要通过抗体依赖的细胞毒作用、补体依赖的细胞毒作用或直接细胞死亡来消除淋巴瘤细胞，但也有一些单抗与恶性细胞用来逃避免疫监视的机制相反。例如，在肿瘤环境中的恶性肿瘤或间质细胞上表达PD-L1会导致T细胞无能。通过单抗靶向PD-1或PD-L1，可以通过解除宿主的内在免疫反应来间接消除癌细胞。单抗靶向治疗的另一种机制是双特异性T细胞结合蛋白(BITE)，如blinatumomab，它直接与宿主免疫细胞结合。这些例子突出了利用被动和主动免疫途径利用单抗针对淋巴瘤表面的广泛可用的治疗方法。其中许多药物已经在临床试验中显示出显著的活性。在这篇综述中，我们将重点介绍新的CD20导向的抗体以及针对CD19、CD22、CD40、CD52和CCR4等新靶点的单抗。此外，我们将回顾单抗解除阻断免疫检查点和咬合blinatumomab。鉴于单抗的成功以及主动和被动免疫疗法的扩大，这些药物将在淋巴瘤的治疗中发挥越来越大的作用。本文的在线版本(doi：10.1186/s13045-0140058-4)包含补充材料，授权用户可以使用。
The CD20-directed monoclonal antibody rituximab established a new era in lymphoma therapy. Since then other epitopes on the lymphoma surface have been identified as potential targets for monoclonal antibodies (mAb). While most mAbs eliminate lymphoma cells mainly by antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity or direct cell death, others counter mechanisms utilized by malignant cells to evade immune surveillance. Expression of PD-L1 on malignant or stromal cells in the tumor environment for example leads to T-cell anergy. Targeting either PD-1 or PD-L1 via mAbs can indirectly eliminate cancer cells by unblocking the host intrinsic immune response. Yet another mechanism of targeted therapy with mAbs are bi-specific T-cell engagers (BiTE) such as blinatumomab, which directly engages the host immune cells. These examples highlight the broad spectrum of available therapies targeting the lymphoma surface with mAbs utilizing both passive and active immune pathways. Many of these agents have already demonstrated significant activity in clinical trials. In this review we will focus on novel CD20-directed antibodies as well as mAbs directed against newer targets like CD19, CD22, CD40, CD52 and CCR4. In addition we will review mAbs unblocking immune checkpoints and the BiTE blinatumomab. Given the success of mAbs and the expansion in active and passive immunotherapies, these agents will play an increasing role in the treatment of lymphomas. The online version of this article (doi:10.1186/s13045-014-0058-4) contains supplementary material, which is available to authorized users.