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从自身抗原中选择表位以在治疗自身免疫性疾病或癌症中引起 Th2 或 Th1 活性。

Selection of epitopes from self-antigens for eliciting Th2 or Th1 activity in the treatment of autoimmune disease or cancer.

机构信息

Tumor Vaccine Group, University of Washington, 850 Republican Street, Box 358050, Seattle, WA, 98109-4714, USA.

EpiThany, Inc., 3240 Fuhrman Ave E, Ste 106, Seattle, WA, 98102, USA.

出版信息

Semin Immunopathol. 2017 Apr;39(3):245-253. doi: 10.1007/s00281-016-0596-7. Epub 2016 Dec 14.

Abstract

Vaccines have been valuable tools in the prevention of infectious diseases, and the rapid development of new vectors against constantly mutating foreign antigens in viruses such as influenza has become a regular, seasonal exercise. Harnessing the immune response against self-antigens is not necessarily analogous or as achievable by iterative processes, and since the desired outcome includes leaving the targeted organism intact, requires some precision engineering. In vaccine-based treatment of autoimmunity and cancer, the proper selection of antigens and generation of the desired antigen-specific therapeutic immunity has been challenging. Both cases involve a threshold of existing, undesired immunity that must be overcome, and despite considerable academic and industry efforts, this challenge has proven to be largely refractory to vaccine approaches leveraging enhanced vectors, adjuvants, and administration strategies. There are in silico approaches in development for predicting the immunogenicity of self-antigen epitopes, which are being validated slowly. One simple approach showing promise is the functional screening of self-antigen epitopes for selective Th1 antitumor immunogenicity, or inversely, selective Th2 immunogenicity for treatment of autoimmune inflammation. The approach reveals the importance of confirming both Th1 and Th2 components of a vaccine immunogen; the two can confound one another if not parsed but may be used individually to modulate antigen-specific inflammation in autoimmune disease or cancer.

摘要

疫苗在预防传染病方面是非常有价值的工具,针对流感等病毒中不断变异的外来抗原,新型载体的快速发展已成为常规的季节性工作。利用针对自身抗原的免疫反应不一定是类似的,也不一定可以通过迭代过程来实现,而且由于所需的结果包括使目标生物体保持完整,因此需要一些精确的工程设计。在基于疫苗的自身免疫和癌症治疗中,正确选择抗原和产生所需的抗原特异性治疗性免疫一直具有挑战性。这两种情况都涉及到必须克服的现有、不需要的免疫的阈值,尽管学术界和工业界做出了相当大的努力,但事实证明,这一挑战在很大程度上难以通过利用增强载体、佐剂和管理策略的疫苗方法来解决。目前正在开发用于预测自身抗原表位免疫原性的计算方法,这些方法正在缓慢验证中。一种简单的方法显示出前景,即针对选择性 Th1 抗肿瘤免疫原性或相反地针对治疗自身免疫炎症的选择性 Th2 免疫原性对自身抗原表位进行功能筛选。该方法揭示了确认疫苗免疫原的 Th1 和 Th2 成分的重要性;如果不进行解析,两者可能会相互混淆,但可以单独用于调节自身免疫性疾病或癌症中的抗原特异性炎症。

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