A Method for Individualizing the Prediction of Immunogenicity of Protein Vaccines and Biologic Therapeutics: Individualized T Cell Epitope Measure (iTEM)
A Method for Individualizing the Prediction of Immunogenicity of Protein Vaccines and Biologic Therapeutics: Individualized T Cell Epitope Measure (iTEM)
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DOI：
10.1155/2010/961752
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发表时间：
2010-01-01
影响因子：
--
通讯作者：
De Groot, Anne S.
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文献类型：
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作者：
Cohen, Tobias;Moise, Leonard;De Groot, Anne S.
药物基因组学的前景取决于预测医学的发展。为了解决免疫学领域的这一需求，我们开发了个体化T细胞表位测量（iTEM）工具，以基于HLA结合预测来估计个体对蛋白质抗原的T细胞应答。在这项研究中，我们使用体外和体内研究的数据验证了前瞻性iTEM预测。我们使用了一个数学公式，将EpiMatrix（一种表位作图工具）生成的DRB 1 * 等位基因结合预测转换为等位基因特异性评分系统。然后，我们证明了iTEM可用于定义HLA结合阈值，高于该阈值可能发生免疫应答，低于该阈值可能不发生免疫应答。当免疫反应集中时，iTEM的预测能力最强，例如在亚单位疫苗接种和蛋白质治疗剂的施用中。iTEM可能是疫苗和蛋白质治疗剂的临床试验设计和临床前评价的有用工具。
The promise of pharmacogenomics depends on advancing predictive medicine. To address this need in the area of immunology, we developed the individualized T cell epitope measure (iTEM) tool to estimate an individual's T cell response to a protein antigen based on HLA binding predictions. In this study, we validated prospective iTEM predictions using data from in vitro and in vivo studies. We used a mathematical formula that converts DRB1* allele binding predictions generated by EpiMatrix, an epitope-mapping tool, into an allele-specific scoring system. We then demonstrated that iTEM can be used to define an HLA binding threshold above which immune response is likely and below which immune response is likely to be absent. iTEM's predictive power was strongest when the immune response is focused, such as in subunit vaccination and administration of protein therapeutics. iTEM may be a useful tool for clinical trial design and preclinical evaluation of vaccines and protein therapeutics.