Combination immune therapies to enhance anti-tumor responses by NK cells.
Combination immune therapies to enhance anti-tumor responses by NK cells.
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DOI：
10.3389/fimmu.2013.00481
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发表时间：
2013-12-23
影响因子：
7.3
通讯作者：
Campbell KS
中科院分区：
文献类型：
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作者：
Mentlik James A;Cohen AD;Campbell KS
自然杀伤 (NK) 细胞是关键的先天免疫淋巴细胞，能够通过靶向细胞毒性破坏病毒感染的细胞或癌细胞，并通过释放炎症细胞因子进一步协助免疫反应。人们认为 NK 细胞通过 FcγRIIIA (CD16) 引导抗体依赖性细胞毒性 (ADCC)，从而有助于某些治疗性单克隆抗体 (mAb) 杀死肿瘤的过程。已经开发出许多治疗性单克隆抗体，它们针对不同的癌症特异性细胞标志物，并可能指导 NK 细胞介导的 ADCC。最近的治疗方法将一些癌症特异性单克隆抗体与其他策略相结合，以优化 NK 细胞的细胞毒性。这些包括针对 NK 细胞激活受体的激动性 mAb 和阻断 NK 细胞抑制性受体以增强 NK 细胞功能的 mAb。此外，一些可以通过其他机制增强 NK 细胞毒性的药物正在与治疗性单克隆抗体联合使用。在这篇综述中，我们研究了用于联合疗法的几种有前景的药物所采用的机制，这些药物可增强 NK 细胞对癌细胞的天然或抗体依赖性细胞毒性，重点是白血病和多发性骨髓瘤的治疗。
Natural killer (NK) cells are critical innate immune lymphocytes capable of destroying virally infected or cancerous cells through targeted cytotoxicity and further assisting in the immune response by releasing inflammatory cytokines. NK cells are thought to contribute to the process of tumor killing by certain therapeutic monoclonal antibodies (mAb) by directing antibody-dependent cellular cytotoxicity (ADCC) through FcγRIIIA (CD16). Numerous therapeutic mAb have been developed that target distinct cancer-specific cell markers and may direct NK cell-mediated ADCC. Recent therapeutic approaches have combined some of these cancer-specific mAb with additional strategies to optimize NK cell cytotoxicity. These include agonistic mAb targeting NK cell activating receptors and mAbs blocking NK cell inhibitory receptors to enhance NK cell functions. Furthermore, several drugs that can potentiate NK cell cytotoxicity through other mechanisms are being used in combination with therapeutic mAb. In this review, we examine the mechanisms employed by several promising agents used in combination therapies that enhance natural or Ab-dependent cytotoxicity of cancer cells by NK cells, with a focus on treatments for leukemia and multiple myeloma.