An immunoinformatics approach for a potential NY-ESO-1 and WT1 based multi-epitope vaccine designing against triple-negative breast cancer.

ABSTRACT

Breast cancer emerges as one of the most prevalent malignancies in women, its incidence showing a concerning upward trend. Among the diverse array of breast cancer subtypes, triple-negative breast cancer (TNBC) assumes notable significance, due to lack of estrogen, progesterone, and HER-2 receptors. More focus has to be placed on creating effective therapy due to the high prevalence and rising incidence of TNBC. Currently, conventional passive treatments have several drawbacks that have not yet been resolved. On the other hand, as innovative immunotherapy approaches, cancer vaccines have offered promising prospects in combatting advanced stages of TNBC. Therefore, the main objective of this study was to utilize WT1 and NY-ESO-1 antigenic proteins in designing a multiepitope vaccine against TNBC. Initially, to generate robust immune responses, we identified antigenic epitopes of both proteins and assessed their immunogenicity. In order to reduce junctional immunogenicity, promiscuous epitopes were joined using the suitable adjuvant (50S ribosomal L7/L12 protein) and incorporated appropriate linkers (GPGPG, AAY, and EAAAK). The best predicted 3D model was refined and validated to achieve an excellent 3D model. Molecular docking analysis and dynamic simulation were conducted to demonstrate the structural stability and integrity of the vaccine/TLR-4 complex. Finally, the vaccine was cloned into the vector pET28 (+). Thus, analysis of the constructed vaccine through immunoinformatics indicates its capability to elicit robust humoral and cellular immune responses in the targeted organism. As such, it holds promise as a therapeutic weapon against TNBC and may open doors for further research in the field.