Design and In Silico Validation of a Novel MZF-1-Based Multi-Epitope Vaccine to Combat Metastatic Triple Negative Breast Cancer

Abstract

Immunotherapy is emerging as a potential therapeutic strategy for triple negative breast cancer (TNBC) owing to the immunogenic landscape of its tumor microenvironment. Interestingly, peptide-based cancer vaccines have garnered a lot of attention as one of the most promising cancer immunotherapy regimens. Thus, the present study intended to design a novel, efficacious peptide-based vaccine against TNBC targeting myeloid zinc finger 1 (MZF1), a transcription factor that has been described as an oncogenic inducer of TNBC metastasis. Initially, the antigenic peptides from MZF1 were identified and evaluated based on their likelihood to induce immunological responses. The promiscuous epitopes were then combined using a suitable adjuvant (50S ribosomal L7/L12 protein) and linkers (AAY, GPGPG, KK, and EAAAK) to reduce junctional immunogenicity. Furthermore, docking and dynamics analyses against TLR-4 and TLR-9 were carried out to understand more about their structural stability and integrity. Finally, the constructed vaccine was subjected to in silico cloning and immune simulation studies. Overall, the findings imply that the designed chimeric vaccine could induce strong humoral and cellular immune responses in the desired organism. In light of these findings, the final multi-epitope vaccine could be used as an effective prophylactic treatment for TNBC and may pave the way for future research.

Keywords

• myeloid zinc finger 1
• triple-negative breast cancer
• immunoinformatics
• vaccine
• immunotherapy
• docking