Computational design and molecular characterization of a multi-epitope peptide vaccine targeting pancreatic cancer

Pancreatic cancer (PC) is a major global health burden, characterized by high mortality rates. Immunotherapy-based strategies have shown promise in combating malignant diseases such as PC. Among these, cancer vaccines are gaining considerable interest as one of the most effective immunotherapeutic approaches. Therefore, in this study, we aimed to develop an effective peptide-based vaccine against PC via immunoinformatic techniques. To construct the vaccine, antigenic proteins associated with PC, including ITGA2, LMAC2, BMPR2, ZFP91, and S100A16, were selected. The predicted epitopes were assembled using proper linkers, and to improve immunogenicity, PADRE and β-defensin 2 sequences were incorporated into the final construct. Further analysis validated the chimeric structure as potentially antigenic, non-allergenic, non-toxic, and soluble. The integrity of its secondary and tertiary structures was also confirmed. Additionally, molecular docking and dynamics simulation of TLR4 demonstrate that the vaccine-receptor complex is structurally stable. The immune simulation results further indicated the vaccines' ability to induce strong cellular and humoral responses. Codon optimization and in silico cloning into an Escherichia coli expression system were also successfully performed. Based on our findings, the proposed vaccine shows promise for targeting PC, warranting further experimental validation in animal models.