Bioimpacts. 2019;9(1):45-56.
doi: 10.15171/bi.2019.06
PMID: 30788259
PMCID: PMC6378095
Scopus id: 85060470196
  Abstract View: 528
  PDF Download: 127
  Full Text View: 57

Original Research

In silico design of a triple-negative breast cancer vaccine by targeting cancer testis antigens

Sepideh Parvizpour 1, Jafar Razmara 2, Mohammad M. Pourseif 1, Yadollah Omidi 1,3 * ORCiD

1 Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Computer Science, Faculty of Mathematical Sciences, University of Tabriz, Tabriz, Iran
3 Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
*Corresponding author: Yadollah Omidi, Email: Email: yomidi@tbzmed.ac.ir

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.

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Submitted: 28 Mar 2018
Revised: 10 Apr 2018
Accepted: 14 Apr 2018
First published online: 02 Jul 2018
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