ABSTRACT

Objectives

The design of peptide-based vaccines for cancer is a promising immunotherapy that can induce a cancer-specific cytotoxic response in tumor cells.

Methods

Herein, we used the immunoinformatic approach in designing a multi-epitope vaccine targeting G-protein coupled receptor 87 (GPCR-87), cystine/glutamate transporter (SLC7A11), Immunoglobulin binding protein 1 (IGBP1), and thioredoxin domain-containing protein 5 (TXNDC5), which can potentially contribute to NSCLC. The MHC-I and MHC-II epitopes selected for the fusion construct were evaluated for their antigenic and non-allergenic natures via VaxiJen and AllerTop.

Results

A total of five epitopes, four class-I (FIFYLKNIV, CRYTSVLFY, RYLKVVKPF, and RQAKIQRYK), and one class-II (NQVRGYPTLLWFRDG), having combined USA population coverage of 100%, were used to make ten possible multi-epitope fusion constructs. In these constructs, PADRE, a universal T-helper epitope, and RSO9, a TLR4 agonist, were fused as adjuvants. The molecular docking analysis revealed that two constructs were showing significant binding affinities toward HLA-A*02:01, the most prevalent HLA allele in USA. Moreover, MD simulations marked one construct as a promising therapeutic candidate.

Conclusion

The multi-epitope vaccine constructs designed using immunogenic, and non-allergenic peptides of NSCLS tumor-associated proteins are likely to pose significant therapeutic efficacies in cancer immunotherapy due to their high binding affinities toward HLA molecules.

中文翻译：

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针对美国人类白细胞抗原背景的非小细胞肺癌 (NSCLC) 多表位疫苗构建体的开发：未来疫苗设计的免疫信息学方法

摘要

目标

基于肽的癌症疫苗的设计是一种很有前途的免疫疗法，可以在肿瘤细胞中诱导癌症特异性细胞毒性反应。

方法

在此，我们使用免疫信息学方法设计了针对 G 蛋白偶联受体 87 (GPCR-87)、胱氨酸/谷氨酸转运蛋白 (SLC7A11)、免疫球蛋白结合蛋白 1 (IGBP1) 和含硫氧还蛋白结构域的蛋白 5 的多表位疫苗（TXNDC5），这可能有助于非小细胞肺癌。通过 VaxiJen 和 AllerTop 评估了为融合构建体选择的 MHC-I 和 MHC-II 表位的抗原性和非过敏性。

结果

共有五个表位，四个 I 类（FIFYLKNIV、CRYTSVLFY、RYLKVVKPF 和 RQAKIQRYK）和一个 II 类（NQVRGYPTLLWRDG），美国人口覆盖率为 100%，用于制造十种可能的多表位融合构建体. 在这些构建体中，将 PADRE（一种通用 T 辅助表位）和 RSO9（一种 TLR4 激动剂）融合为佐剂。分子对接分析显示，两种构建体对HLA -A*02:01（美国最普遍的HLA等位基因）显示出显着的结合亲和力。此外，MD 模拟将一个构建体标记为有希望的治疗候选者。

结论

使用 NSCLS 肿瘤相关蛋白的免疫原性和非过敏性肽设计的多表位疫苗构建体可能在癌症免疫治疗中具有显着的治疗效果，因为它们对HLA分子具有高结合亲和力。