title: Metadherin peptides containing CD4(+) and CD8(+) T cell epitopes as a therapeutic vaccine candidate against cancer.
abstract: The concept of peptide-based vaccines against cancer has made noteworthy progress. Metadherin (MTDH) overexpression and its role in the development of diverse cancers make it an attractive target for cancer immunotherapy. In the current study, six different T cell epitope prediction tools were run to identify MTDH peptides with multiple immunogenic regions. Further, molecular docking was performed to assess HLA-peptide binding interactions. Nine and eleven peptides fragments containing multiple CD8 (+) and CD4 (+) T-cell epitopes, ranging from 9 to 20 amino acids, respectively, were obtained using a consensus immunoinformatics approach. The three peptides that were finally identified as having overlapping CD4 (+) and CD8 (+) T- cell epitopes are ARLREMLSVGLGFLRTELG, FLLGYGWAAACAGAR, YIDDEWSGLNGLSSADP. These peptides were found to not only have multiple T cell epitopes but also to have binding affinity with wide HLA molecules. A molecular docking study revealed that the predicted immunogenic peptides (with single or multiple T cell epitopes) of MTDH have comparable binding energies with naturally bound peptides for both HLA classes I and II. Thus, these peptides have the potential to induce immune responses that could be considered for developing synthetic peptide vaccines against multiple cancers.
authors.affiliation: Department of Biotechnology, Thapar University, Bhadson Road, Patiala, Punjab, India.
authors.forename: Gourav
authors.initials: G
authors.lastname: Dhiman
authors.affiliation: Department of Biotechnology, Thapar University, Bhadson Road, Patiala, Punjab, India.
authors.forename: Neha
authors.initials: N
authors.lastname: Lohia
authors.affiliation: Department of Biotechnology, Thapar University, Bhadson Road, Patiala, Punjab, India.
authors.forename: Sahil
authors.initials: S
authors.lastname: Jain
authors.affiliation: Department of Biotechnology, Thapar University, Bhadson Road, Patiala, Punjab, India. manoj.baranwal@thapar.edu, baranwal.manoj@gmail.com.
authors.forename: Manoj
authors.initials: M
authors.lastname: Baranwal
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding; D011487:Protein Conformation; D016601:RNA-Binding Proteins
chemical_list: D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C483039:MTDH protein, human; D008565:Membrane Proteins; D010455:Peptides; D016601:RNA-Binding Proteins
keywords: immunoinformatics; molecular docking; tumor antigen; vaccine