Abstract
Introduction: Triple-negative breast cancer (TNBC) is an
important subtype of breast cancer, which occurs in the
absence of estrogen, progesterone and HER-2 receptors.
According to the recent studies, TNBC may be a cancer
testis antigen (CTA)-positive tumor, indicating that the
CTA-based cancer vaccine can be a treatment option
for the patients bearing such tumors. Of these antigens
(Ags), the MAGE-A family and NY-ESO-1 as the most
immunogenic CTAs are the potentially relevant targets
for the development of an immunotherapeutic way of the
breast cancer treatment.
Methods: In the present study, immunoinformatics
approach was used to design a multi-epitope peptide vaccine to combat the TNBC. The vaccine
peptide was constructed by the fusion of three crucial components, including the CD8+ cytotoxic T
lymphocytes (CTLs) epitopes, helper epitopes and adjuvant. The epitopes were predicted from the
MAGE-A and NY-ESO-1 Ags. In addition, the granulocyte-macrophage-colony-stimulating factor
(GM-CSF) was used as an adjuvant to promote the CD4+ T cells towards the T-helper for more
strong induction of CTL responses. The components were conjugated by proper linkers.
Results: The vaccine peptide was examined for different physiochemical characteristics to confirm
the safety and immunogenic behavior. Furthermore, the 3D-structure of the vaccine peptide was
predicted based on the homology modeling approach using the MODELLER v9.17 program. The
vaccine structure was also subjected to the molecular dynamics simulation study for structure
refinement. The results verified the immunogenicity and safety profile of the constructed vaccine
as well as its capability for stimulating both the cellular and humoral immune responses.
Conclusion: Based on our in-silico analyses, the proposed vaccine may be considered for the
immunotherapy of TNBC.