Identification and Design of a Next-Generation Multi Epitopes Bases Peptide Vaccine Candidate Against Prostate...

Prostate cancer (PCa) is the second most diagnosed cancer in men and ranked fifth in overall cancer diagnosis. During the past decades, it has arisen as a significant life-threatening disease in men at an older age. At the early onset of illness when it is in localized form, radiation and surgical treatments are applied against this disease. In case of adverse situations androgen deprivation therapy, chemotherapy, hormonal therapy, etc. are widely used as a therapeutic element. However, studies found the occurrences of several side effects after applying these therapies. In current work, several immunoinformatic techniques were applied to formulate a multi-epitopic vaccine from the overexpressed antigenic proteins of PCa. A total of 13 epitopes were identified from the five prostatic antigenic proteins (PSA, PSMA, PSCA, STEAP, and PAP), after validation with several in silico tools. These epitopes were fused to form a vaccine element by (GGGGS)₃ peptide linker. Afterward, 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) was used as an adjuvant to initiate and induce STING-mediated cytotoxic cascade. In addition, molecular docking was performed between the vaccine element and HLA class I antigen with the low ACE value of -251 kcal/mol which showed a significant binding. Molecular simulation using normal mode analysis (NMA) illustrated the docking complex as a stable one. Therefore, this observation strongly indicated that our multi epitopes bases peptide vaccine molecule will be an effective candidate for the treatment of the PCa.