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Immunopeptidome screening to design An immunogenic construct against PRAME positive breast cancer; An in silico study
- Source :
- Computational biology and chemistry. 85
- Publication Year :
- 2019
-
Abstract
- Background Metastasis is the main cause of breast cancer (BC) lethality, especially in early stages, led to improvements in therapeutic procedures. Lately, by improvements in our perception of biological processes and immune system new classes of vaccines are emerged that grant us the opportunity of designing resolute constructs against desired antigens. In the current study, we used a variety of immunoinformatics tools to design a novel cancer vaccine against Preferentially Expressed Antigen of Melanoma (PRAME), which counts as a cancer testis antigen for various human cancers including BC. The PRAME up-regulation leads to strengthen BC stem cells maintenance, drug resistance, cell survival, adaptation, and apoptosis evading in cancerous cells. Methods and results The PRAME co-expressed genes were mined and validated through BC RNA-sequencing of TCGA data. The immunodominant T-cell predicted epitopes were fused and engineered to form the vaccine. The safety, allergenicity, and immunogenic capabilities of the vaccine were confirmed by promising immunoinformatics tools. The vaccine’s structure was verified to be hydrophilic in most areas through Kyte and Doolittle hydrophobicity plotting. The interactions between the designed vaccine and immune receptors of TLR4 and IL1R were confirmed by protein-protein docking after modeling its tertiary structure. Finally, codon optimization and in silico cloning were performed to guarantee better in-vivo results. Conclusion In conclusion, concerning in silico assessments’ results in this study, the designed vaccine can potentially boost immune responses against PRAME, therefore may decrease BC development and metastasis. According to the mined PRAME co-expressed genes and their functional annotation, cell cycle regulation is the prime mechanism opted by this construct and its adjacent regulatory genes along boosting immune reactions.
- Subjects :
- 0301 basic medicine
In silico
Breast Neoplasms
Computational biology
Biology
Biochemistry
Cancer Vaccines
Epitope
Metastasis
Antigen-Antibody Reactions
03 medical and health sciences
0302 clinical medicine
Immune system
Antigen
Structural Biology
Antigens, Neoplasm
medicine
Humans
PRAME
Organic Chemistry
Computational Biology
medicine.disease
Computational Mathematics
030104 developmental biology
030220 oncology & carcinogenesis
Cancer/testis antigens
Female
Cancer vaccine
Peptides
Subjects
Details
- ISSN :
- 1476928X
- Volume :
- 85
- Database :
- OpenAIRE
- Journal :
- Computational biology and chemistry
- Accession number :
- edsair.doi.dedup.....2cb356f7d486ee64068cc13b3a9174f5