Banham Alison H, Pulford Karen
University of Oxford, John Radcliffe Hospital, Nuffield Department of Clinical Laboratory Sciences, Headington, Oxford, UK.
Expert Opin Ther Pat. 2009 Jul;19(7):1023-8. doi: 10.1517/13543770902785183.
CD4(+)CD25(+) regulatory T cells (Tregs) regulate immunotolerance. Treg depletion causes autoimmune disease, whereas Treg expansion can prevent effective immunosurveillance of 'non-self' antigens in many clinical settings, including cancer.
Patent WO2008081581 presents an invention to target Tregs therapeutically via vaccination with immunogenic peptides from the forkhead box P3 (FOXP3) transcription factor. Our objective was the scientific evaluation of this patent and advantages versus potential risks of this therapeutic strategy.
There are 432 patents on Tregs and a diverse array of approaches for their therapeutic targeting; these have already been reviewed elsewhere. This article focuses on the utility of the selected peptides for specifically targeting FOXP3, whether FOXP3 expression is Treg specific and the likely effectiveness versus risk of autoimmunity relating to FOXP3-targeted immunotherapy.
RESULTS/CONCLUSIONS: Our analysis of the immunogenic FOXP3 peptides found many (10/21) with significant (i.e. only one or two amino-acid differences) or complete identity with other proteins; these are not suitable for specific FOXP3 targeting. Some peptides have the ability to target specific FOXP3 isoforms. FOXP3 vaccination might be an effective method for reducing Treg numbers in cancer patients. However, this must be balanced against the risks of developing autoimmunity and targeting effector T cells.
CD4(+)CD25(+)调节性T细胞（Tregs）调节免疫耐受。Treg耗竭会导致自身免疫性疾病，而在包括癌症在内的许多临床环境中，Treg扩增会妨碍对“非自身”抗原进行有效的免疫监视。
专利WO2008081581提出了一项发明，即通过用叉头框P3（FOXP3）转录因子的免疫原性肽进行疫苗接种来对Tregs进行治疗性靶向。我们的目的是对该专利进行科学评估，并评估这种治疗策略的优势与潜在风险。
关于Tregs及其治疗性靶向的方法有432项专利；这些已在其他地方进行了综述。本文重点关注所选肽对FOXP3进行特异性靶向的效用、FOXP3表达是否具有Treg特异性以及与FOXP3靶向免疫治疗相关的自身免疫的可能有效性与风险。
结果/结论：我们对免疫原性FOXP3肽的分析发现，许多肽（10/21）与其他蛋白质具有显著（即只有一两个氨基酸差异）或完全相同的序列；这些不适用于FOXP3的特异性靶向。一些肽具有靶向特定FOXP3异构体的能力。FOXP3疫苗接种可能是降低癌症患者Treg数量的有效方法。然而，这必须与发生自身免疫和靶向效应T细胞的风险相权衡。
