通过疫苗学方法设计一种新的非小细胞肺癌多表位肽疫苗:一项计算机研究

IF 1.5 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Biology Research Communications Pub Date : 2022-03-01 DOI:10.22099/mbrc.2022.42468.1697
A/Prof. Fatemeh Heidary MD, MPH, FAAO, FICO, M. Tourani, Fatemeh Hejazi-Amiri, S. H. Khatami, N. Jamali, Mortaza Taheri‐Anganeh
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引用次数: 1

摘要

肺癌是世界上最常见的肿瘤类型。非小细胞肺癌(NSCLC)被认为是任何上皮细胞相关的肺癌,占所有肺癌病例的85%以上。与SCLC相比,NSCLC对化疗的反应较差。因此,对其他治疗方法的需求变得更加明显,近年来免疫治疗作为一种有前景的治疗方法得到了越来越多的关注。本研究旨在设计一种多表位肽疫苗,靶向在肿瘤细胞增殖侵袭中起主要作用的SP17、AKAP4和PTTG1的主要癌/睾丸抗原。考虑到B细胞表位和CD4和CD8诱导的表位是对癌细胞应答最重要的细胞,通过严格的免疫信息学分析和多个免疫系统参数的研究构建了该蛋白疫苗。通过对密码子的反翻译和优化,验证了所设计蛋白的克隆和在大肠杆菌中的表达潜力。评估了物理化学、抗原和致敏性特征,以确认疫苗的安全性和免疫原性。预测了二级和三级结构。最后,对模型进行内在失序和三维模型精化验证,消除结构问题。所设计的结构具有稳定的结构,可以作为抗原刺激免疫系统,而不是过敏原。所建模型三维结构有效、稳定。在用于非小细胞肺癌患者之前,需要进一步的研究来批准这种新疫苗的安全性和免疫原性。
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Design of a new multi-epitope peptide vaccine for non-small cell Lung cancer via vaccinology methods: an in silico study
Lung cancer is the most common type of tumor worldwide. Non-small-cell lung carcinoma (NSCLC) is considered any epithelial cell-related lung cancer, which includes more than 85% of all lung cancer cases. NSCLC is less responsive to chemotherapy than SCLC. Therefore, the need for other treatments has become more pronounced and immunotherapy has gained increasing attention as a promising therapy in recent years. The current study aimed to design a multi-epitope peptide vaccine targeting main cancer/testis antigens of SP17, AKAP4, and PTTG1, which have a major function in tumor cell proliferation invasion. The protein vaccine was constructed using the rigorous immunoinformatics analysis and investigation of several immune system parameters, considering B cell epitopes and CD4 and CD8 induced epitopes as the most important cells to respond to cancer cells. Inverse translation and optimization of codons were performed to have the designed protein's cloning as well as expression potential in E.coli. Physicochemical, antigenic, and allergenic features were assessed to confirm the safety and immunogenicity of the vaccine. The secondary and tertiary structures were predicted. Finally, intrinsic disorder and 3D model refinement and validation were performed to eliminate structural problems. The designed construct had a stable structure that could be an antigen and stimulate the immune system and not be an allergen. The built model 3D structure was valid and stable. Further investigations are needed to approve the safety and immunogenic property of this new vaccine for NSCLC before it can be used in patients.
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来源期刊
Molecular Biology Research Communications
Molecular Biology Research Communications BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
3.00
自引率
0.00%
发文量
12
期刊介绍: “Molecular Biology Research Communications” (MBRC) is an international journal of Molecular Biology. It is published quarterly by Shiraz University (Iran). The MBRC is a fully peer-reviewed journal. The journal welcomes submission of Original articles, Short communications, Invited review articles, and Letters to the Editor which meets the general criteria of significance and scientific excellence in all fields of “Molecular Biology”.
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