Mahdavi Manijeh, Moreau Violaine, Kheirollahi Majid
Genetic and Molecular biology Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
CNRS UMR5048-UM-INSERM U1054, Centre de Biochimie Structurale, 29 rue de Navacelles, 34090 Montpellier Cedex, France.
J Mol Graph Model. 2017 Aug;75:316-321. doi: 10.1016/j.jmgm.2017.06.004. Epub 2017 Jun 8.
The insulin-like growth factor-1 receptor (IGF-1R) plays a key role in proliferation, growth, differentiation, and development of several human malignancies including breast and pancreatic adenocarcinoma. IGF-1R targeted immunotherapeutic approaches are particularly attractive, as they may potentially elicit even stronger antitumor responses than traditional targeted approaches. Cancer peptide vaccines can produce immunologic responses against cancer cells by triggering helper T cell (Th) or cytotoxic T cells (CTL) in association with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells. In our previous study, we set a technique based on molecular docking in order to find the best MHC class I and II binder peptides using GOLD. In the present work, molecular docking analyses on a library consisting of 30 peptides mimicking discontinuous epitopes from IGF-1R extracellular domain identified peptides 249 and 86, as the best MHC binder peptides to both MHC class I and II molecules. The receptors most often targeted by peptide 249 are HLA-DR4, HLA-DR3 and HLA-DR2 and those most often targeted by peptide 86 are HLA-DR4, HLA-DP2 and HLA-DR3. These findings, based on bioinformatics analyses, can be conducted in further experimental analyses in cancer therapy and vaccine design.
胰岛素样生长因子-1受体(IGF-1R)在包括乳腺癌和胰腺腺癌在内的多种人类恶性肿瘤的增殖、生长、分化和发育过程中发挥着关键作用。针对IGF-1R的免疫治疗方法特别有吸引力,因为它们可能比传统的靶向方法引发更强的抗肿瘤反应。癌症肽疫苗可以通过与抗原呈递细胞表面的主要组织相容性复合体(MHC)I类或II类分子结合,触发辅助性T细胞(Th)或细胞毒性T细胞(CTL),从而产生针对癌细胞的免疫反应。在我们之前的研究中,我们基于分子对接技术,使用GOLD软件寻找最佳的MHC I类和II类结合肽。在目前的工作中,对一个由30个模拟IGF-1R细胞外结构域不连续表位的肽组成的文库进行分子对接分析,确定肽249和86是与MHC I类和II类分子结合的最佳肽。肽249最常靶向的受体是HLA-DR4、HLA-DR3和HLA-DR2,肽86最常靶向的受体是HLA-DR4、HLA-DP2和HLA-DR3。基于生物信息学分析的这些发现,可以在癌症治疗和疫苗设计的进一步实验分析中进行验证。