Introduction: Breast cancer is the second-leading cause of cancer death and a major health risk for women. More than 40,000 deaths are expected in the United States in 2016, although recent advances in early detection have improved overall survival. The successful treatment of breast cancer in the last 10 to 15 years is one of the greatest achievements of medical science, especially in oncology, and is considered a medical revolution. Therefore, like other cancers, it is inevitable to deal with this type of disease to enable early diagnosis and effective treatment, where immunotoxins have a special place in targeted therapy. Immunotoxins have been used to treat cancer. The immunotoxin binds to the surface antigen of the cancer cell, enters the cell by endocytosis, and destroys the cancer cell
Methods: In addition, the recognition of specific antigens on the surface of cancer cells, the constituents of this type of drug and its composition based on peptide bonds, and the creation of recombinant proteins were among the requirements investigated in this bioinformatic, structural, and functional research. The properties of membrane antigens on the surface of breast cancer cells were evaluated using Docking, Modeller, and Gromacs software, as well as online protein structure prediction databases such as the Swiss Model and Protein Atlas
Results: The results of this research in the first stage led to the discovery of 10 antigens with the ability to bind to the surface of breast cancer cells with the highest and most specific expression of the EGFR antigen and, on the other hand, protein molecules that can bind. INS was selected as the most efficient ligand for this antigen. Next, the assembly of toxin from Pseudomonas with a selective ligand using the AAASGG 3 (GGGGS) linker in six modes resulted in six recombinant structures of different quality. The structures, among them the first structural model of the best protein in terms of structure and function, showed affinity and immunogenicity after exposure to realistic conditions. In general, the results of this research led to the introduction of the EGFR antigen as a suitable candidate for effective immunotoxins against the breast and the creation of an effective immunotoxin against this antigen with favorable structural and functional capabilities.
Conclusion: Hence, the targeted treatment of cancer through immunotoxin with the confirmation of the patent sequence led to the creation of a recombinant structure, which was analyzed with bioinformatics software. To ensure accurate results in the laboratory, we utilized Escherichia coli strain DH5 as a host during the cloning phase for plasmid DNA replication. This enabled a more precise and reliable replication process, thereby confirming the validity of our computational modeling, and the results of this research led to the modeling and simulation of the engineering structure of Cetuximab ZZpe38 immunotoxin. For future research, gene expression in mammalian cells will be the focus
Keywords: Breast cancer, toxin, ligand, EGFR antigen, immunotoxin drug