Modulating ion channel function with antibodies and nanobodies.
Modulating ion channel function with antibodies and nanobodies.
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DOI：
10.1016/j.coi.2018.02.003
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发表时间：
2018-06
影响因子：
7
通讯作者：
C. Stortelers;Carolina Pinto-Espinoza;D. van Hoorick;F. Koch-Nolte
中科院分区：
文献类型：
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作者：
C. Stortelers;Carolina Pinto-Espinoza;D. van Hoorick;F. Koch-Nolte
snp小体是来源于骆驼重链抗体的抗原结合结构域。离子通道拮抗纳米体和抗体有望成为抗炎药。纳米体具有选择性高、显影性好、半衰期可延长等特点。纳米体可以靶向裂缝，并连接成结合多个表位的格式。近年来，针对Kv1的功能性阻断纳米体已被开发出来。3和P2X7。免疫细胞表达各种电压门控和配体门控离子通道，介导带电离子在质膜上的内流和外排，从而控制膜电位，介导细胞内信号转导通路。因此，这些通道为免疫反应的实验性调节和免疫疾病的治疗干预提供了潜在的靶点。作用于离子通道的小分子药物和天然毒素已经证明了靶向免疫细胞离子通道的潜在治疗益处。然而，不良的副作用和免疫原性阻碍了这些分子的应用。由于其高特异性、低免疫原性和有益的药效学，针对膜和分泌蛋白的抗体已成为肿瘤和炎症的有效治疗药物。纳米体——源自天然存在于骆驼体内的重链抗体的单结构域片段——与抗体相比具有额外的优势，包括突出到隐式表位和容易形成多特异性试剂。本文综述了近年来针对免疫细胞离子通道的抗体和纳米体的开发和应用进展。
HighlightsNanobodies are antigen-binding domains derived from camelid heavy chain antibodies.Ion channel antagonizing nanobodies and antibodies hold promise as anti-inflammatories.Nanobodies feature high selectivity, good developability, and extendable half life.Nanobodies can target clefts and be linked into formats that bind multiple epitopes.Functional blocking Nanobodies have been developed recently against Kv1. 3 and P2X7.Immune cells express various voltage-gated and ligand-gated ion channels that mediate the influx and efflux of charged ions across the plasma membrane, thereby controlling the membrane potential and mediating intracellular signal transduction pathways. These channels thus present potential targets for experimental modulation of immune responses and for therapeutic interventions in immune disease. Small molecule drugs and natural toxins acting on ion channels have illustrated the potential therapeutic benefit of targeting ion channels on immune cells. Unwanted side effects and immunogenicity have however hampered the application of these molecules. Owing to their high specificity, low immunogenicity and beneficial pharmacodynamics, antibodies targeting membrane and secretory proteins have emerged as potent therapeutics in oncology and inflammation. Nanobodies—single domain fragments derived from heavy chain antibodies naturally occurring in camelids—offer additional benefits versus antibodies, including protrusion into cryptic epitopes and easy formatting of multi-specific reagents. Here we review recent progress in the development and application of antibodies and Nanobodies targeting ion channels on immune cells.