Designing a novel multi-epitope T vaccine for 'targeting protein for Xklp-2' (TPX2) in hepatocellular carcinoma based on immunoinformatics approach
Autor: | Amin Rostami, Zarrin Minuchehr, Farzaneh Afzali, Bijan Bambai, Parisa Ghahremanifard, Zahra Nayeri |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
010405 organic chemistry
Helper T lymphocyte medicine.medical_treatment In silico Immunogenicity Bioengineering Biology medicine.disease 01 natural sciences Biochemistry Protein tertiary structure Epitope 0104 chemical sciences Analytical Chemistry CTL Cancer immunotherapy Hepatocellular carcinoma Drug Discovery medicine Cancer research Molecular Medicine Cytotoxic T cell Adjuvant |
DOI: | 10.1101/570952 |
Popis: | 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 was performed to calculate the free energy 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. |
Databáze: | OpenAIRE |
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