Design and evaluation of a multiepitope vaccine for pancreatic cancer using immune-dominant epitopes derived from the signature proteome in expression datasets.
Antigenicity
Immunotherapy
Molecular dynamics simulations
Multi-epitope vaccine
Pancreatic cancer
Transcriptomics
Journal
Medical oncology (Northwood, London, England)
ISSN: 1559-131X
Titre abrégé: Med Oncol
Pays: United States
ID NLM: 9435512
Informations de publication
Date de publication:
24 Mar 2024
24 Mar 2024
Historique:
received:
06
11
2023
accepted:
14
02
2024
medline:
24
3
2024
pubmed:
24
3
2024
entrez:
24
3
2024
Statut:
epublish
Résumé
Pancreatic cancer is a highly aggressive and often lethal malignancy with limited treatment options. Its late-stage diagnosis and resistance to conventional therapies make it a significant challenge in oncology. Immunotherapy, particularly cancer vaccines, has emerged as a promising avenue for treating pancreatic cancer. Multi-epitope vaccines, designed to target multiple epitopes derived from various antigens associated with pancreatic cancer, have gained attention as potential candidates for improving therapeutic outcomes. In this study, we have explored transcriptomics and protein expression databases to identify potential upregulated proteins in pancreatic cancer cells. After examining a total of 21,054 proteins from various databases, it was discovered that 143 proteins expressed differently in malignant and healthy cells. The CTL, HTL and BCE epitopes were predicted for the shortlisted proteins. 51,840 vaccine constructs were created by concatenating CTL, HTL, and B-cell epitopes in the respective sequences. The best 86 structures were selected from a set of 51,840 designs after they were analyzed for vaxijenicity, allergenicity, toxicity, and antigenicity scores. In further simulation of the immune response using constructs, it was found that 41417, 37961, and 40841 constructs could produce a strong immune response when injected. Further, it was found that construct 37961 showed stronger interaction and stability with TLR-9 as determined from the large-scale molecular dynamics simulations. Moreover, the 37961 construct has shown interactions with TLR-9 suggests its potential in inducing immune response. In addition, construct 37961 has shown 100% predicted solubility in the E. coli expression system. Overall, the study indicates the designed construct 37961 has the potential to induce an anti-tumor immune response and long-standing protection pending further studies.
Identifiants
pubmed: 38522058
doi: 10.1007/s12032-024-02334-4
pii: 10.1007/s12032-024-02334-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
90Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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