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首页> 外文期刊>Gene Therapy and Molecular Biology >In silico analysis of chimeric polytope ofcancer/testis antigens for dendritic cell-basedimmune-gene therapy applications
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In silico analysis of chimeric polytope ofcancer/testis antigens for dendritic cell-basedimmune-gene therapy applications

机译：基于树突状细胞的免疫基因治疗应用的癌症/睾丸抗原嵌合多表位的计算机分析

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Background: Cancer cells benefit from different biological processes that allow them to grow successfully even in the presence of native defense mechanisms. The development of effective cancer vaccines could benefit from in silico techniques that evaluate tumor cell biology. Cancer/testis antigens (CTAs) exhibit limited expression patterns in normal human germ line and placenta cells, while overexpression of CTAs has been reported frequently in a variety of cancer cell types. Among CTAs, MAGEA4, LAGE1, and NY-ESO1, which are highly overexpressed in esophageal squamous cell carcinomas, may have crucial roles in tumor cell progression and metastasis.Results: In this study we designed a synthetic chimeric gene encoding the MHC class-I HLA-restricted epitopes of MAGEA4, LAGE1, and NY-ESO1. This polytope molecule was designed based on human codon optimization. The epitopes were linked using five hydrophobic amino acid repeats. The structure of the synthetic gene, related mRNA, deduced protein, and their stabilities were analyzed by bioinformatic software. Furthermore, the cleavage sites, T- cell epitopes, and MHC-binding affinity of peptides in the construct were predicted using web-based servers. The solvent accessibility and post-translational modifications of the construct’s protein were also predicted.Conclusion: A new combination of antigenic epitopes of CTAs, which may define accessibility, solubility, and immunogenicity, is presented to develop a chimeric gene as an effective structural model for cancer immune-gene therapy.
机译：背景：癌细胞受益于不同的生物过程，即使存在天然防御机制，癌细胞也能成功生长。有效的癌症疫苗的开发可受益于评估肿瘤细胞生物学的计算机技术。癌症/睾丸抗原（CTA）在正常人生殖细胞和胎盘细胞中显示有限的表达模式，而在多种癌细胞类型中，CTAs的过表达则屡见报道。在食管鳞癌中，在食管鳞状细胞癌中过度表达的MAGEA4，LAGE1和NY-ESO1在肿瘤细胞的进展和转移中可能起着至关重要的作用。结果：在这项研究中，我们设计了编码I类MHC的合成嵌合基因。 HLA限制的MAGEA4，LAGE1和NY-ESO1抗原决定簇。该多表位分子是基于人密码子优化设计的。使用五个疏水氨基酸重复序列连接表位。通过生物信息学软件分析了合成基因的结构，相关的mRNA，推导的蛋白质及其稳定性。此外，使用基于网络的服务器预测了构建物中肽的切割位点，T细胞表位和MHC结合亲和力。结论：还提出了CTAs抗原表位的新组合，可以定义可及性，溶解性和免疫原性，以开发嵌合基因作为有效的结构模型。癌症免疫基因疗法。

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