Khalili Saeed, Rahbar Mohammad Reza, Dezfulian Mohammad Haj, Jahangiri Abolfazl
Department of Medical Biotechnology, Tarbiat Modares University, Tehran, Iran.
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Molecular Biology, Saadati Pathobiology Laboratory, Shiraz, Iran.
J Theor Biol. 2015 Aug 21;379:66-78. doi: 10.1016/j.jtbi.2015.04.026. Epub 2015 Apr 30.
Predefined and pre-weighted objective criteria and essential role of Wilms׳ tumor wild type gene (WT1) for maintaining transformed features of cancer cells confirm the high potency of WT1 as a valuable cancer antigen. The antigen was at the top of the ranking among 75 representative cancer antigens. In the present study, an in silico approach was launched to characterized novel CTL epitopes and design a novel multi-epitope DNA vaccine to elicit a desirable immune response against cancers over expressing WT1. Forty-four novel epitopes were described. A multi-epitope construct was designed based on predicted epitopes which is 310 residues in length. The vaccine candidate designed here displays acceptable population coverage (>65%) in different ethnicities as well as high probability of eliciting WT1 antibodies which both are pertinent goals in the context of appropriate multi-epitope vaccines. Various in silico analyses indicate that final vaccine is a qualified immunotherapy candidate capable of eliciting both CD4+ and CD8+ T cell responses.
预先定义和预先加权的客观标准以及肾母细胞瘤野生型基因（WT1）在维持癌细胞转化特征方面的重要作用，证实了WT1作为一种有价值的癌症抗原具有高效力。该抗原在75种代表性癌症抗原中排名第一。在本研究中，采用计算机模拟方法来鉴定新型CTL表位，并设计一种新型多表位DNA疫苗，以引发针对过度表达WT1的癌症的理想免疫反应。描述了44种新型表位。基于预测的表位设计了一种多表位构建体，其长度为310个残基。此处设计的候选疫苗在不同种族中显示出可接受的人群覆盖率（>65%），以及引发WT1抗体的高概率，这两者都是合适的多表位疫苗背景下的相关目标。各种计算机模拟分析表明，最终疫苗是一种合格的免疫治疗候选物，能够引发CD4+和CD8+ T细胞反应。
