Expanding the targets available to therapeutic antibodies via novel disease-specific markers.

Expanding the targets available to therapeutic antibodies via novel disease-specific markers.
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DOI:
10.3109/08830185.2011.608136
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发表时间:
2011-10
影响因子:
5
通讯作者:
Hildebrand WH
Hildebrand WH
中科院分区:
医学3区
文献类型:
--
作者:
Weidanz JA;Hildebrand WH

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免疫疗法的发展为癌症和感染性疾病的临床应用提供了重要的前景。在这里,我们描述了一种新的,综合的免疫治疗方法,结合新的技术来发现和靶向疾病特异性肽/HLA I类复合物。这类独特的标记物使整个蛋白质组可用于抗体试剂,并为靶向癌细胞和感染细胞提供无与伦比的特异性。我们的三臂方法之一使用了一种创新技术,用于有效,直接发现新的肽/HLA I类标记物。第二组应用强大的和创造性的策略来产生T细胞受体模拟物(TCRms),其是对肽/HLA I类标志物具有精确结合特异性的抗体,并使用TCRms来验证癌细胞和感染细胞上标志物的特异性表达。我们方法的第三个分支使用TCRms以高灵敏度和特异性靶向并杀死患病细胞。总之,两种开创性技术的结合扩大了可被治疗性抗体靶向的疾病特异性标志物的库,并实现了基于HLA的免疫治疗的强大的综合方法。
The development of immunotherapies offers significant promise for clinical applications in cancer and infectious diseases. Here we describe a novel, integrated approach to immunotherapy that combines novel technologies to discover and target disease-specific peptide/HLA class I complexes. This unique class of markers makes the entire proteome accessible to antibody reagents and offers unsurpassed specificity for targeting cancerous and infected cells. Arm one of our three-armed approach uses an innovative technology for the efficient, direct discovery of new peptide/HLA class I markers. Arm two applies a powerful and inventive strategy to generate T cell receptor mimics (TCRms), which are antibodies with exquisite binding specificity for peptide/HLA class I markers, and uses TCRms to validate the specific expression of markers on cancerous and infected cells. The third arm of our approach uses TCRms to target and kill diseased cells with high sensitivity and specificity. In summary, the combination of two pioneering technologies expands the repertoire of disease-specific markers that can be targeted by therapeutic antibodies and enables a powerful, integrated approach to HLA-based immunotherapy.
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