Immunoinformatics analysis of Wilms’ Tumor Protein to Design Multiepitope Peptide-Based Vaccine Against Breast Cancer for Indonesian Population

Abstract

Breast cancer is one of the leading cancer-related deaths among females in Indonesia. The use of cancer vaccine as immunotherapy to elicit T-cell responses such as CD8+ cytotoxic T-cells (CTL) and CD4+ helper T-cells (HTL) is on the rise. CTL will kill cancer cells and HTL will orchestrate the immune responses to cancer. T-cell recognises peptide antigen as a complex with HLA molecule on the surface of the cancer cells. Effective induction of protective T-cell immunity with the absence of autoimmunity required specific target antigens that are overexpressed in tumor cells but not in healthy cells. In this study, Wilms' tumor protein 1 (WT1) was proposed as the target for the cancer vaccine since it is overexpressed in breast cancer cells. The immunoinformatics tools netCTLpan and netMHCIIpan were employed to identify WT1 CTL and HTL epitopes, respectively. The epitopes were specifically predicted as peptides that bind to HLA alleles predominant in the Indonesian population to design a vaccine for this populat ion. The peptides generated were then evaluated for the immunogenicity and the ability to induce IFNγ production. Vaccine constructs containing the selected promiscuous CTL and HTL epitopes were assembled using appropriate peptide linkers and maltose-binding protein (MBP) was used as the adjuvant. Further in-silico evaluation showed that the vaccine construct is antigenic, non-allergenic, able to elicit CTL and HTL responses, and covers 99.95% of the Indonesian population. The current insilico analysis results can be used as the basis for developing a multiepitope peptide-based vaccine for breast cancer in Indonesia.