Department of Biotechnology, National Institute of Technology-Warangal, Warangal, Telangana, 506004, India.
Med Oncol. 2024 Mar 24;41(5):90. doi: 10.1007/s12032-024-02334-4.
Pancreatic cancer is a highly aggressive and often lethal malignancy with limited treatment options. Its late-stage diagnosis and resistance to conventional therapies make it a significant challenge in oncology. Immunotherapy, particularly cancer vaccines, has emerged as a promising avenue for treating pancreatic cancer. Multi-epitope vaccines, designed to target multiple epitopes derived from various antigens associated with pancreatic cancer, have gained attention as potential candidates for improving therapeutic outcomes. In this study, we have explored transcriptomics and protein expression databases to identify potential upregulated proteins in pancreatic cancer cells. After examining a total of 21,054 proteins from various databases, it was discovered that 143 proteins expressed differently in malignant and healthy cells. The CTL, HTL and BCE epitopes were predicted for the shortlisted proteins. 51,840 vaccine constructs were created by concatenating CTL, HTL, and B-cell epitopes in the respective sequences. The best 86 structures were selected from a set of 51,840 designs after they were analyzed for vaxijenicity, allergenicity, toxicity, and antigenicity scores. In further simulation of the immune response using constructs, it was found that 41417, 37961, and 40841 constructs could produce a strong immune response when injected. Further, it was found that construct 37961 showed stronger interaction and stability with TLR-9 as determined from the large-scale molecular dynamics simulations. Moreover, the 37961 construct has shown interactions with TLR-9 suggests its potential in inducing immune response. In addition, construct 37961 has shown 100% predicted solubility in the E. coli expression system. Overall, the study indicates the designed construct 37961 has the potential to induce an anti-tumor immune response and long-standing protection pending further studies.
胰腺癌是一种高度侵袭性且常常致命的恶性肿瘤，治疗选择有限。其晚期诊断和对传统疗法的耐药性使其成为肿瘤学领域的重大挑战。免疫疗法，特别是癌症疫苗，已成为治疗胰腺癌的一种有前途的方法。多表位疫苗旨在针对源自与胰腺癌相关的各种抗原的多个表位，已成为改善治疗效果的潜在候选药物。在这项研究中，我们探讨了转录组学和蛋白质表达数据库，以确定胰腺癌细胞中潜在的上调蛋白。在检查了来自各种数据库的总共 21054 种蛋白质后，发现 143 种蛋白质在恶性和健康细胞中表达不同。针对这些蛋白质预测了 CTL、HTL 和 BCE 表位。通过在相应序列中串联 CTL、HTL 和 B 细胞表位，共构建了 51840 种疫苗构建体。在对一组 51840 个设计进行了 vaxijenicity、变应原性、毒性和抗原性评分分析后，从这组设计中选择了最佳的 86 个结构。在使用构建体进一步模拟免疫反应时，发现当注射时，构建体 41417、37961 和 40841 可以产生强烈的免疫反应。此外，从大规模分子动力学模拟中发现，构建体 37961 与 TLR-9 表现出更强的相互作用和稳定性。此外，构建体 37961 与 TLR-9 的相互作用表明其在诱导免疫反应方面的潜力。此外，构建体 37961 已显示出在大肠杆菌表达系统中具有 100%预测的可溶性。总的来说，这项研究表明，所设计的构建体 37961 具有诱导抗肿瘤免疫反应和长期保护的潜力，有待进一步研究。
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