Simulation of chimeric IL2-HER-2-IFNγ vaccine against breast cancer

Background: Breast cancer is a leading cause of cancer-related deaths in women worldwide and there is no effective therapy for patients with invasive and metastatic breast cancer. Immunotherapy may be proved effective in treating patients with advanced breast cancer. We have designed a complex immunogen derived from major antigen breast cancer, human HER- 2/neu-(480–620)that represents a three-dimensional epitope and nearly whole ofIFNγ sequence(24 -161)andIL2sequence(21-153) as an vaccine for expression in plants. Methods:Related sequences of HER-2,IL2and IFNγ were obtained from UniProtKB/Swiss-Prot.The physico-chemical properties were analyzed using the Expasy'sProtParam software.Segments were selected based on prediction ofimmunogenic epitopes. Linear B-cell epitopes of construct were estimated by bcepred.Discotope1.2 was employed topredict discontinuous B-cell epitopes.In general, epitopes having VaxiJen cutoff values of >0.5 was selected.For Tcellepitopeprediction. MHC2Pred was employed to predict peptides from the protein binding with MHCII. The chimeric construct codons were optimized based on plant host by EMBOSS .The mRNA secondary structure of the gene was evaluated by the mfold software . The prediction of the secondary structure of the protein was performed using the GORIV.The I-TASSER was employed for tertiary structure prediction.The tool AccelrysDiscoveryStudio2.5 was used tovisualize the modeled3D structures.3Dstructural stability of the protein was evaluated by Swiss-PdbViewer software forenergy minimization. AlgPred software was used to predict the allergenicity of the protein. Results:All of the results suggest that the construct can be an appropriate vaccine candidate against Breast cancer. Conclusion:Before working in lab we should be confident about the validity of vaccine throw in silico analyses

کلیدواژه ها:

Breast Cancer ، Chimeric vaccine ، IFNγ ، IL2 ، Her2