Design of a Novel Recombinant Multi-Epitope Vaccine against Triple-Negative Breast Cancer
Hassan Dariushnejad1,2, Vajihe Ghorbanzadeh2, Soheila Akbari3
1Department of Medical Biotechnology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
Background:
Triple-negative breast cancer (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 Carcinoembryonic antigen (CEA), Metadherin (MTDH), and Mucin 1 (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.
Insights
A novel cancer vaccine targeting triple-negative breast cancer (TNBC) was designed using immunoinformatics. This therapeutic candidate shows promise for treating advanced TNBC by targeting Carcinoembryonic antigen (CEA), Metadherin (MTDH), and Mucin 1 (MUC-1).
Area of Science:
- Immunology
- Bioinformatics
- Oncology
Background:
- Triple-negative breast cancer (TNBC) lacks ERBB2, estrogen, and progesterone receptors.
- Cancer vaccines represent a novel immunotherapy for advanced TNBC.
- Evaluating Carcinoembryonic antigen (CEA), Metadherin (MTDH), and Mucin 1 (MUC-1) as TNBC vaccine candidates.
Purpose of the Study:
- Design a novel therapeutic vaccine against TNBC.
- Utilize immunoinformatics and bioinformatics for vaccine development.
- Assess the potential of CEA, MTDH, and MUC-1 as vaccine targets.
Main Methods:
- Selected immunodominant epitopes from CEA, MTDH, and MUC-1.
- Incorporated recombinant TLR4 agonists as adjuvants.
- Employed computational methods including 3D modeling, docking, and molecular simulations.
Main Results:
- Bioinformatics and immunoinformatics evaluations support the vaccine construct's efficacy.
- The designed vaccine demonstrated acceptable quality through computational analysis.
Conclusions:
- The designed vaccine is a promising therapeutic candidate against TNBC.
- Further in vitro and in vivo studies are warranted to confirm its effectiveness.
