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Design of a Novel Recombinant Multi-Epitope Vaccine against Triple-Negative Breast Cancer

BACKGROUND: TNBC is determined by the absence of ERBB2, estrogen and progesterone receptors’ expression. Cancer vaccines, as the novel immunotherapy strategies, have emerged as promising tools for treating the advanced stage of TNBC. The aim of this study was to evaluate CEA, MTDH, and MUC-1 protein...

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Autores principales: Dariushnejad, Hassan, Ghorbanzadeh, Vajihe, Akbari, Soheila, Hashemzadeh, Pejman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Pasteur Institute of Iran 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987416/
https://www.ncbi.nlm.nih.gov/pubmed/35090304
http://dx.doi.org/10.52547/ibj.26.2.160
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author Dariushnejad, Hassan
Ghorbanzadeh, Vajihe
Akbari, Soheila
Hashemzadeh, Pejman
author_facet Dariushnejad, Hassan
Ghorbanzadeh, Vajihe
Akbari, Soheila
Hashemzadeh, Pejman
author_sort Dariushnejad, Hassan
collection PubMed
description BACKGROUND: TNBC is determined by the absence of ERBB2, estrogen and progesterone receptors’ expression. Cancer vaccines, as the novel immunotherapy strategies, have emerged as promising tools for treating the advanced stage of TNBC. The aim of this study was to evaluate CEA, MTDH, and MUC-1 proteins as vaccine candidates against TNBC. METHODS: In this research, a novel vaccine was designed against TNBC by using different immunoinformatics and bioinformatics approaches. Effective immunodominant epitopes were chosen from three antigenic proteins, namely CEA, MTDH, and MUC-1. Recombinant TLR4 agonists were utilized as an adjuvant to stimulate immune responses. Following the selection of antigens and adjuvants, appropriate linkers were chosen to generate the final recombinant protein. To achieve an excellent 3D model, the best predicted 3D model was required to be refined and validated. To demonstrate whether the vaccine/TLR4 complex is stable or not, we performed docking analysis and dynamic molecular simulation. RESULT: Immunoinformatics and bioinformatics evaluations of the designed construct demonstrated that this vaccine candidate could effectively be used as a therapeutic armament against TNBC. CONCLUSION: Bioinformatics studies revealed that the designed vaccine has an acceptable quality. Investigating the effectiveness of this vaccine can be confirmed by supplementary in vitro and in vivo studies.
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spelling pubmed-89874162022-04-19 Design of a Novel Recombinant Multi-Epitope Vaccine against Triple-Negative Breast Cancer Dariushnejad, Hassan Ghorbanzadeh, Vajihe Akbari, Soheila Hashemzadeh, Pejman Iran Biomed J Full Length BACKGROUND: TNBC is determined by the absence of ERBB2, estrogen and progesterone receptors’ expression. Cancer vaccines, as the novel immunotherapy strategies, have emerged as promising tools for treating the advanced stage of TNBC. The aim of this study was to evaluate CEA, MTDH, and MUC-1 proteins as vaccine candidates against TNBC. METHODS: In this research, a novel vaccine was designed against TNBC by using different immunoinformatics and bioinformatics approaches. Effective immunodominant epitopes were chosen from three antigenic proteins, namely CEA, MTDH, and MUC-1. Recombinant TLR4 agonists were utilized as an adjuvant to stimulate immune responses. Following the selection of antigens and adjuvants, appropriate linkers were chosen to generate the final recombinant protein. To achieve an excellent 3D model, the best predicted 3D model was required to be refined and validated. To demonstrate whether the vaccine/TLR4 complex is stable or not, we performed docking analysis and dynamic molecular simulation. RESULT: Immunoinformatics and bioinformatics evaluations of the designed construct demonstrated that this vaccine candidate could effectively be used as a therapeutic armament against TNBC. CONCLUSION: Bioinformatics studies revealed that the designed vaccine has an acceptable quality. Investigating the effectiveness of this vaccine can be confirmed by supplementary in vitro and in vivo studies. Pasteur Institute of Iran 2022-03 2022-01-29 /pmc/articles/PMC8987416/ /pubmed/35090304 http://dx.doi.org/10.52547/ibj.26.2.160 Text en https://creativecommons.org/licenses/by/3.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/ (https://creativecommons.org/licenses/by/3.0/) ) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Length
Dariushnejad, Hassan
Ghorbanzadeh, Vajihe
Akbari, Soheila
Hashemzadeh, Pejman
Design of a Novel Recombinant Multi-Epitope Vaccine against Triple-Negative Breast Cancer
title Design of a Novel Recombinant Multi-Epitope Vaccine against Triple-Negative Breast Cancer
title_full Design of a Novel Recombinant Multi-Epitope Vaccine against Triple-Negative Breast Cancer
title_fullStr Design of a Novel Recombinant Multi-Epitope Vaccine against Triple-Negative Breast Cancer
title_full_unstemmed Design of a Novel Recombinant Multi-Epitope Vaccine against Triple-Negative Breast Cancer
title_short Design of a Novel Recombinant Multi-Epitope Vaccine against Triple-Negative Breast Cancer
title_sort design of a novel recombinant multi-epitope vaccine against triple-negative breast cancer
topic Full Length
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987416/
https://www.ncbi.nlm.nih.gov/pubmed/35090304
http://dx.doi.org/10.52547/ibj.26.2.160
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