Design of a new structure of immunogenic chimeric polytope against human various cancers using immunoinformatics and structural methods

Autor: Saeed Pirmoradi
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Basic & Clinical Cancer Research, Vol 15, Iss 1 (2024)
Druh dokumentu: article
ISSN: 2228-6527
2228-5466
Popis: Cancer is one of the deadliest diseases in recent decades. Which has different types. Despite advances in the treatment of cancer, they are still the most critical threat to public health. Although conventional therapies have played a major role in the treatment or eradication of the disease, the emergence of emerging diseases requires new therapies such as vaccine design. Significant challenges in cancer drug treatment such as drug resistance and side effects of drug toxicity and high cost have made the treatment process more difficult. The aim of this study was to design a new and effective strategy for preparing a vaccine against cancer using some antigenic proteins in this disease. After preparing appropriate epitopes of antigenic protein compounds in cancers and examining their antigenic and immunogenic properties, the process of fusion vaccine composition was performed with the help of various bioinformatics tools to study the physicochemical properties and two-dimensional and three-dimensional structures and Their validation as well as immunological and simulation properties were investigated and finally the codons of vaccine constructs were optimized to increase the translation rate of its cloning process in the expression vector pET28a (+) to evaluate the expression of protein in prokaryotic cells in E. coli K12 system. Finally, the docking process was performed with some receptors that are effective in immunological processes in the body, such as TLRs, MHCI, and MHCII. Selected epitopes of physiologically important cancer proteins theoretically cover a high percentage of the world's population. The vaccine was designed with a stable, antigenic, and non-sensitizing composition. Structural analysis of the TRL5/vaccine binding complex and its simulation process reveal sufficiently stable critical with the prospect of receptor recognition. The dynamics of the immune response, having the potential to stimulate and produce active and memory B cells, and the production of CD8+T, and CD4+T cells show a favorable role in stimulating and creating effective immune responses by Th2 and Th1 cells. Computational results using bioinformatics tools showed that our designed immunogenic structure has the potential to stimulate cellular and humoral immune responses against cancer properly. Therefore, based on these data and after evaluating the effectiveness of the candidate vaccine through in vivo and in vitro immunological tests, it can be suggested as a candidate vaccine against cancer.
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