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应用免疫信息学方法设计针对神经胶质瘤的肽疫苗。

Peptide vaccine design against glioblastoma by applying immunoinformatics approach.

机构信息

Department of Computer Science, Faculty of Mathematics, Statistics, and Computer Science, University of Tabriz, Tabriz, Iran.

Department of Computer Science, Faculty of Mathematics, Statistics, and Computer Science, University of Tabriz, Tabriz, Iran.

出版信息

Int Immunopharmacol. 2024 Dec 5;142(Pt B):113219. doi: 10.1016/j.intimp.2024.113219. Epub 2024 Sep 27.

DOI:10.1016/j.intimp.2024.113219
PMID:39340993
Abstract

Brain tumors are considered to be one of the most fatal forms of cancer owing to their highly aggressive attributes, diverse characteristics, and notably low rate of survival. Among these tumors, glioblastoma stands out as the prevalent and perilous variant Despite the present advancements in surgical procedures, pharmacological treatment, and radiation therapy, the overall prognosis remains notably unfavorable, as merely 4.3 % of individuals manage to attain a five-year survival rate; For this reason, it has emerged as a challenge for cancer researchers. Therefore, among several immunotherapy methods, using peptide-based vaccines for cancer treatment is considered promising due to their ability to generate a focused immune response with minimal damage. This study endeavors to devise a multi-epitope vaccine utilizing an immunoinformatics methodology to address the challenge posed by glioblastoma disease. Through this approach, it is anticipated that the duration and expenses associated with vaccine manufacturing can be diminished, while simultaneously enhancing the characteristics of the vaccine. The target gene in this research is ITGA5, which was achieved through TCGA analysis by targeting the PI3K-Akt pathway as a significant association with patient survival. Subsequently, the suitable epitopes of T and B cells were selected through various immunoinformatics tools by analyzing their sequence. Then, nine epitopes were merged with GM-CSF as an adjuvant to enhance immunogenicity. The outcomes encompass molecular docking, molecular dynamics (MD) simulation, simulation of the immune response, prognosis and confirmation of the secondary and tertiary structure, Chemical and physical characteristics, toxicity, as well as antigenicity and allergenicity of the potential vaccine candidate against glioblastoma.

摘要

脑肿瘤被认为是最致命的癌症形式之一,因为它们具有高度侵袭性、多样的特征和明显较低的生存率。在这些肿瘤中,胶质母细胞瘤是最常见和最危险的变异。尽管目前在手术程序、药物治疗和放射治疗方面取得了进展,但总体预后仍然明显不利,只有 4.3%的人能够达到五年生存率;因此,它已成为癌症研究人员的一个挑战。因此,在几种免疫疗法中,使用基于肽的疫苗治疗癌症被认为是有前途的,因为它们能够产生具有最小损伤的集中免疫反应。本研究旨在利用免疫信息学方法设计一种多表位疫苗,以应对胶质母细胞瘤疾病带来的挑战。通过这种方法,预计可以减少疫苗制造的时间和费用,同时提高疫苗的特性。本研究的靶基因是 ITGA5,通过 TCGA 分析靶向 PI3K-Akt 通路实现,该通路与患者生存有显著关联。随后,通过分析序列,使用各种免疫信息学工具选择合适的 T 和 B 细胞表位。然后,将 9 个表位与 GM-CSF 融合作为佐剂,以增强免疫原性。研究结果包括针对胶质母细胞瘤的潜在疫苗候选物的分子对接、分子动力学 (MD) 模拟、免疫反应模拟、预后以及二级和三级结构的确认、化学和物理特性、毒性以及抗原性和变应原性。

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