Parvizpour Sepideh, Razmara Jafar, Pourseif Mohammad M, Omidi Yadollah
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Computer Science, Faculty of Mathematical Sciences, University of Tabriz, Tabriz, Iran.
Bioimpacts. 2019;9(1):45-56. doi: 10.15171/bi.2019.06. Epub 2018 Jul 2.
Triple-negative breast cancer (TNBC) is an important subtype of breast cancer, which occurs in the absence of estrogen, progesterone and HER-2 receptors. According to the recent studies, TNBC may be a cancer testis antigen (CTA)-positive tumor, indicating that the CTA-based cancer vaccine can be a treatment option for the patients bearing such tumors. Of these antigens (Ags), the MAGE-A family and NY-ESO-1 as the most immunogenic CTAs are the potentially relevant targets for the development of an immunotherapeutic way of the breast cancer treatment. In the present study, immunoinformatics approach was used to design a multi-epitope peptide vaccine to combat the TNBC. The vaccine peptide was constructed by the fusion of three crucial components, including the CD8+ cytotoxic T lymphocytes (CTLs) epitopes, helper epitopes and adjuvant. The epitopes were predicted from the MAGE-A and NY-ESO-1 Ags. In addition, the granulocyte-macrophage-colony-stimulating factor (GM-CSF) was used as an adjuvant to promote the CD4+ T cells towards the T-helper for more strong induction of CTL responses. The components were conjugated by proper linkers. The vaccine peptide was examined for different physiochemical characteristics to confirm the safety and immunogenic behavior. Furthermore, the 3D-structure of the vaccine peptide was predicted based on the homology modeling approach using the MODELLER v9.17 program. The vaccine structure was also subjected to the molecular dynamics simulation study for structure refinement. The results verified the immunogenicity and safety profile of the constructed vaccine as well as its capability for stimulating both the cellular and humoral immune responses. Based on our in-silico analyses, the proposed vaccine may be considered for the immunotherapy of TNBC.
三阴性乳腺癌（TNBC）是乳腺癌的一种重要亚型，其发生时不存在雌激素、孕激素和HER-2受体。根据最近的研究，TNBC可能是一种癌胚抗原（CTA）阳性肿瘤，这表明基于CTA的癌症疫苗可能是此类肿瘤患者的一种治疗选择。在这些抗原（Ag）中，MAGE-A家族和NY-ESO-1作为免疫原性最强的CTA，是开发乳腺癌免疫治疗方法的潜在相关靶点。在本研究中，采用免疫信息学方法设计了一种多表位肽疫苗来对抗TNBC。该疫苗肽由三个关键成分融合而成，包括CD8+细胞毒性T淋巴细胞（CTL）表位、辅助表位和佐剂。这些表位是从MAGE-A和NY-ESO-1抗原中预测出来的。此外，粒细胞-巨噬细胞集落刺激因子（GM-CSF）被用作佐剂，以促进CD4+T细胞向辅助性T细胞分化，从而更强烈地诱导CTL反应。这些成分通过合适的连接子连接。对疫苗肽进行了不同的物理化学特性检测，以确认其安全性和免疫原性。此外，使用MODELLER v9.17程序基于同源建模方法预测了疫苗肽的三维结构。还对疫苗结构进行了分子动力学模拟研究以优化结构。结果验证了所构建疫苗的免疫原性和安全性以及其刺激细胞免疫和体液免疫反应的能力。基于我们的计算机模拟分析，所提出的疫苗可考虑用于TNBC的免疫治疗。
