Designing a novel SOX9 based multi-epitope vaccine to combat metastatic triple-negative breast cancer using immunoinformatics approach

Abstract

Immunotherapies are a promising treatment option especially for the management of TNBC owing to its higher levels of tumour-associated antigens together with higher mutational load. Of note, the administration of preventive vaccines in the early stage of the cancer holds promise for effective disease management. Therefore, the present study aimed to develop a novel multi-epitope peptide-based vaccination against TNBC employing SOX9, which has recently been recognized as a key regulator of TNBC metastasis. The immunodominant regions from the SOX9 protein were computed and assessed based on their ability to elicit both T and B lymphocyte mediated responses. The resultant epitopes were fused using appropriate linkers (EAAAK, KK, AAY and GPGPG) and adjuvant (50S ribosomal protein L7/L12) to enhance the vaccine’s immunogenicity. The physicochemical properties and population coverage were also anticipated for the constructed vaccine. Adding together, docking and dynamics simulation studies were performed on the modelled vaccine against TLR-4 to provide insight into the stability. Finally, the designed vaccine was cloned into the pET28 (+) vector and immunological simulation studies were carried out. These results demonstrate that our designed vaccine had the potency to trigger humoral and cellular immune responses. Based on these collective evidences, the final proposed vaccine could be an interesting therapeutics for the management of TNBC in the near future. Graphical abstract Schematic representation of an efficient vaccine design framework by combining the range of immunoinformatics strategies. Supplementary Information The online version contains supplementary material available at 10.1007/s11030-022-10539-w.

The Construction of A Multi-epitope Vaccine Against Klebsiella pneumoniae Using in silico Approach

“…This linker also has a rigid helical structure. 20 Whereas the KK, GPGPG, and AAY linkers are hydrophilic amino acids and can prevent domain function disturbances and vaccine folding. The GPGPG linker can stimulate the HTL response and conformation of the bound immunogenicity of HTL, while the AAY linker can increase epitope presentation and eliminate junctional epitopes.…”

Progress of related drugs and new drugs for immunotherapy of triple-negative breast cancer

“…Sema4A is a signaling protein recently identified as a major regulatory factor in TNBC progression; MZF1 is a transcription factor and a carcinogenic inducer of TNBC metastasis; SOX9 is also considered a key regulatory factor in TNBC metastasis. Using appropriate adjuvants and epitope combinations, these research teams identified and evaluated the potential of antigen peptide-induced immune responses against Sema4A, MZF1, and SOX9, and conducted immune simulation studies and computer cloning on the constructed vaccines, indicating that in the target organisms, the designed chimeric vaccines can elicit robust humoral and cellular immunological responses [29][30][31]. Based on this evidence, these types of vaccines may become a promising therapy for TNBC in the future.…”

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

“…Dar et al (2022) implemented a reverse vaccinology approach to determine the immunogenic B, CTL, and HTL epitopes from NT5E, ANPEP, and MME proteins, the putative targets for gallbladder cancer (GBC), and developed a robust peptide-based vaccine against GBC [ 19 ]. Importantly, our team successfully developed an immunoinformatics-based peptide vaccine targeting SOX9, a transcription factor that has been reported as a major regulator of TNBC metastasis [ 20 ]. With these frames of reference, the present study intended to develop a subunit vaccine integrating immunoinformatics methods and simulation studies targeting MZF-1, a recently reported oncogenic inducer, pertaining to the treatment of TNBC patients.…”