考虑到免疫学事实的VEGFR2和c-MET的计算机分析:对乳腺癌mRNA疫苗设计的意义

IF 4.7 2区 医学 Q2 IMMUNOLOGY
International immunopharmacology Pub Date : 2025-10-30 Epub Date: 2025-08-09 DOI:10.1016/j.intimp.2025.115315
Marziyeh Ghayoumian, Fahimeh Shamsi, Hamid Madanchi, Mohammad Mehdi Ranjbar, Reza Jalalirad, Ramin Sarrami Forooshani, Mehdi Mahdavi
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引用次数: 0

摘要

主动免疫在肿瘤治疗中可以诱导肿瘤特异性免疫反应而不损害正常细胞。在这些方法中,特别是在fda批准的mRNA疫苗成功之后,该平台作为一种有前途的策略获得了更多的关注。这项研究的重点是设计一种基于mrna的乳腺癌疫苗,通过免疫信息学方法选择两种在乳腺癌细胞中过表达的血管生成元件。根据抗原性、毒性和过敏原对表位进行筛选,以确保它们能同时引发T细胞和b细胞介导的免疫反应。分子对接模拟分析了它们与主要组织相容性复合体(MHC)分子的相互作用。最终的疫苗构建包括10个选择的表位,它们与合适的连接物连接,并优化了密码子的使用,确保了理想的GC含量和密码子适应指数。蛋白质对接分析显示出与合适结合能的强相互作用,而分子动力学模拟证实了对接复合物的稳定性。免疫模拟显示抗体滴度高,细胞因子反应,免疫细胞如B细胞、细胞毒性T淋巴细胞(CTL)细胞和辅助T淋巴细胞(HTL)细胞增加。基于这些发现,这种疫苗设计为基于mrna的乳腺癌疫苗提供了强有力的候选疫苗,目前正在进一步开发中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In silico analysis of VEGFR2 and c-MET in consideration with immunologic facts: Implications for mRNA vaccine design against breast cancer.

Active immunization in cancer therapy can induce tumor-specific immune responses without harming the normal cells. Among these approaches, especially after the success of FDA-approved mRNA vaccines, this platform has gained much more attention as a promising strategy. This study focused on designing an mRNA-based vaccine against breast cancer by selecting two angiogenic elements that are overexpressed in breast cancer cells, in an immunoinformatic approach. Epitopes were filtered based on antigenicity, toxicity, and allergenicity to ensure that they could elicit both T and B-cell-mediated immune responses. Molecular docking simulations analyzed their interactions with Major Histocompatibility Complex (MHC) molecules. The final vaccine construct included 10 selected epitopes linked with appropriate linkers and optimized for codon usage, ensuring ideal GC content and codon adaptation index. Protein docking analyses showed strong interactions with appropriate binding energies, while molecular dynamics simulations confirmed the docked complex stability. Immune simulations revealed high antibody titers, cytokine response, and an increase in immune cells such as B Cells, Cytotoxic T Lymphocyte (CTL) cells, and Helper T Lymphocyte (HTL) cells. Based on these findings, this vaccine design presents a strong candidate for an mRNA-based breast cancer vaccine, with further development currently underway.

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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
期刊介绍: International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.
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