Designing a Novel Multi-epitope T Vaccine for “Targeting Protein for Xklp-2” (TPX2) in Hepatocellular Carcinoma Based on Immunoinformatics Approach
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Hepatocellular carcinoma (HCC) is one of the leading cancer-related deaths worldwide. Recently, studies for HCC treatment are focused on cancer immunotherapy, particularly cancer vaccines, to complete and assist other therapies. TPX2 is a microtubule-associated protein necessary for cell division; therefore, alteration in its expression, especially up regulation, is associated with several human carcinomas such as HCC. In this study, immunoinformatics tools were used to design a rational multi-epitope T vaccine against TPX2 in HCC. Cytotoxic T lymphocytes (CTL) and Helper T lymphocytes (HTL) epitopes were predicted and Maltose-binding protein (MBP) was added to the construct as an adjuvant. Evaluation of vaccine properties was indicated that our construct is stable and immunogenic enough to induce relevant responses besides not being allergic. After predicting the tertiary structure and energy minimization, protein–protein docking and molecular dynamics were performed to calculate the free energy and stability of possible interactions between the vaccine and toll-like receptor 4 (TLR4) to assure that simultaneous complementary responses would be activated by our construct. Finally, Codon optimization and in silico cloning were performed to ensure the vaccine expression efficiency in the desired host.
KeywordsConstruct Hepatocellular cancer Immunogenicity Immunotherapeutic In-silico
Hepatitis B virus
Hepatitis C virus
Cytotoxic T lymphocytes
Targeting protein for Xklp-2
Helper T lymphocytes
Major histocompatibility complex
Grand average of hydropathicity
- E. coli
Java Codon Adaptation Tool
Codon Adaptation Index
Root mean square deviation
Root mean square fluctuation
The financial support of this research project by the National Institute of Genetic Engineering and Biotechnology (NIGEB) of Iran is acknowledged. Also, we would like to thank Dr. Javad Zamani for his contribution in this article.
ZM, BB and PGH conceptualized the project. FA and P.GH did the analyses and interpreted the data except the data related to docking part which was done by ZN and FA. PGH and AR wrote the manuscript. ZM supported the project (corresponding author). All authors read and approved the final manuscript.
Compliance with Ethical Standards
Conflict of interest
There is no conflict of interest.
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