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Design of a Novel Recombinant Multi-Epitope Vaccine against Triple-Negative Breast Cancer
Authors:Hassan Dariushnejad  Vajihe Ghorbanzadeh  Soheila Akbari  Pejman Hashemzadeh
Institution:1.Department of Medical Biotechnology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran; 2.Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran; 3.Department of Obstetrics and Gynecology, Lorestan University of Medical Sciences, Khorramabad, Iran
Abstract: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.Key Words: Adjuvants, Triple-negative breast cancer, Vaccine
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