Design of a Humanized Immunotoxin Based on Pertuzumab-Derived scFv and Shiga-Like Toxin 2 Subunit A Against Breast Cancer: An In Silico Study
Background and purpose: Breast cancer is the second cause of mortality among women. HER2, a member of the epidermal growth factor receptor family, is overexpressed in approximately 25% of breast cancer cases. This receptor represents a valuable therapeutic target in the management of breast cancer....
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Mazandaran University of Medical Sciences
2025-05-01
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| Series: | Journal of Mazandaran University of Medical Sciences |
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| Online Access: | http://jmums.mazums.ac.ir/article-1-21452-en.pdf |
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| author | Zeinab Ghesmati Khadijeh Ahmadi Navid Nezafat Farzaneh Vahedi Mortaza Taheri-Anganeh Seyyed Hossein Khatami Hasan Ghasemi Rahmatollah Soltani Vahid Zarezade Ahmad Movahedpour Ahmad Movahedpour |
| author_facet | Zeinab Ghesmati Khadijeh Ahmadi Navid Nezafat Farzaneh Vahedi Mortaza Taheri-Anganeh Seyyed Hossein Khatami Hasan Ghasemi Rahmatollah Soltani Vahid Zarezade Ahmad Movahedpour Ahmad Movahedpour |
| author_sort | Zeinab Ghesmati |
| collection | DOAJ |
| description | Background and purpose: Breast cancer is the second cause of mortality among women. HER2, a member of the epidermal growth factor receptor family, is overexpressed in approximately 25% of breast cancer cases. This receptor represents a valuable therapeutic target in the management of breast cancer. For the treatment of HER2-positive breast cancer, several agents, including trastuzumab (Herceptin), have been approved. Herceptin is a monoclonal antibody capable of binding to the HER2 receptor. A single-chain variable fragment (scFv) derived from Herceptin can also be utilized in the development of immunotoxins targeting HER2-positive cancer cells. Shiga toxins are bacterial exotoxins commonly produced by Shigella dysenteriae and certain strains of Escherichia coli. The A subunit of Shiga-like toxin 2 (Stx2A) is a potent cytotoxic agent with the potential to kill cancer cells.
Materials and methods: In this insilico study, we employed bioinformatics tools to design an immunotoxin composed of a HER2-specific single-chain variable fragment (scFv) and the A subunit of Shiga-like toxin 2. To construct the immunotoxin, the amino acid sequences of the scFv and Shiga-like toxin 2 subunit A were joined via a peptide linker. The secondary structure, physicochemical properties, solubility, and potential allergenicity of the construct were predicted. The tertiary structure of the immunotoxin was modeled, refined, and evaluated. Protein-protein docking was performed to assess immunotoxin-receptor binding, and molecular dynamics simulations were used to evaluate immunotoxin stability.
Results: According to the findings, the designed construct appears to be a stable protein with adequate solubility, non-allergenic properties, and a structurally favorable configuration for binding to HER2.
Conclusion: In conclusion, the designed construct demonstrates potential for the production of a HER2-targeted immunotoxin. However, further validation through comprehensive in vitro and in vivo immunological assays is necessary to confirm the efficacy and therapeutic potential of the construct. |
| format | Article |
| id | doaj-art-c7e584bb06b44428aeee29a94e2bb275 |
| institution | OA Journals |
| issn | 1735-9260 1735-9279 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Mazandaran University of Medical Sciences |
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| series | Journal of Mazandaran University of Medical Sciences |
| spelling | doaj-art-c7e584bb06b44428aeee29a94e2bb2752025-08-20T02:10:24ZengMazandaran University of Medical SciencesJournal of Mazandaran University of Medical Sciences1735-92601735-92792025-05-01352451529Design of a Humanized Immunotoxin Based on Pertuzumab-Derived scFv and Shiga-Like Toxin 2 Subunit A Against Breast Cancer: An In Silico StudyZeinab Ghesmati0Khadijeh Ahmadi1Navid Nezafat2Farzaneh Vahedi3Mortaza Taheri-Anganeh4Seyyed Hossein Khatami5Hasan Ghasemi6Rahmatollah Soltani7Vahid Zarezade8Ahmad Movahedpour9Ahmad Movahedpour10 PhD in Molecular Medicine, Department of Molecular Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Assistant Professor, Infectious and Tropical Diseases Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran Assistant Professor, Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran PhD in Medical Biotechnology, Cellular and Molecular Research Center, Babol University of Medical Sciences, Babol, Iran Assistant Professor, Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran PhD in Clinical Biochemistry, Department of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Associate Professor, Department of Basic Sciences, Abadan University of Medical Sciences, Abadan, Iran Assistant Professor, Department of Basic Sciences, Behbahan Faculty of Medical Sciences, Behbahan, Iran Assistant Professor, Department of Basic Sciences, Behbahan Faculty of Medical Sciences, Behbahan, Iran Assistant Professor, Department of Basic Sciences, Abadan University of Medical Sciences, Abadan, Iran Assistant Professor, Cellular and Molecular Research Center, Yasouj University of Medical Sciences, Yasouj, Iran Background and purpose: Breast cancer is the second cause of mortality among women. HER2, a member of the epidermal growth factor receptor family, is overexpressed in approximately 25% of breast cancer cases. This receptor represents a valuable therapeutic target in the management of breast cancer. For the treatment of HER2-positive breast cancer, several agents, including trastuzumab (Herceptin), have been approved. Herceptin is a monoclonal antibody capable of binding to the HER2 receptor. A single-chain variable fragment (scFv) derived from Herceptin can also be utilized in the development of immunotoxins targeting HER2-positive cancer cells. Shiga toxins are bacterial exotoxins commonly produced by Shigella dysenteriae and certain strains of Escherichia coli. The A subunit of Shiga-like toxin 2 (Stx2A) is a potent cytotoxic agent with the potential to kill cancer cells. Materials and methods: In this insilico study, we employed bioinformatics tools to design an immunotoxin composed of a HER2-specific single-chain variable fragment (scFv) and the A subunit of Shiga-like toxin 2. To construct the immunotoxin, the amino acid sequences of the scFv and Shiga-like toxin 2 subunit A were joined via a peptide linker. The secondary structure, physicochemical properties, solubility, and potential allergenicity of the construct were predicted. The tertiary structure of the immunotoxin was modeled, refined, and evaluated. Protein-protein docking was performed to assess immunotoxin-receptor binding, and molecular dynamics simulations were used to evaluate immunotoxin stability. Results: According to the findings, the designed construct appears to be a stable protein with adequate solubility, non-allergenic properties, and a structurally favorable configuration for binding to HER2. Conclusion: In conclusion, the designed construct demonstrates potential for the production of a HER2-targeted immunotoxin. However, further validation through comprehensive in vitro and in vivo immunological assays is necessary to confirm the efficacy and therapeutic potential of the construct.http://jmums.mazums.ac.ir/article-1-21452-en.pdfbreast cancershiga-like toxin 2 subunit aherceptinher2bioinformaticsimmunotoxin |
| spellingShingle | Zeinab Ghesmati Khadijeh Ahmadi Navid Nezafat Farzaneh Vahedi Mortaza Taheri-Anganeh Seyyed Hossein Khatami Hasan Ghasemi Rahmatollah Soltani Vahid Zarezade Ahmad Movahedpour Ahmad Movahedpour Design of a Humanized Immunotoxin Based on Pertuzumab-Derived scFv and Shiga-Like Toxin 2 Subunit A Against Breast Cancer: An In Silico Study Journal of Mazandaran University of Medical Sciences breast cancer shiga-like toxin 2 subunit a herceptin her2 bioinformatics immunotoxin |
| title | Design of a Humanized Immunotoxin Based on Pertuzumab-Derived scFv and Shiga-Like Toxin 2 Subunit A Against Breast Cancer: An In Silico Study |
| title_full | Design of a Humanized Immunotoxin Based on Pertuzumab-Derived scFv and Shiga-Like Toxin 2 Subunit A Against Breast Cancer: An In Silico Study |
| title_fullStr | Design of a Humanized Immunotoxin Based on Pertuzumab-Derived scFv and Shiga-Like Toxin 2 Subunit A Against Breast Cancer: An In Silico Study |
| title_full_unstemmed | Design of a Humanized Immunotoxin Based on Pertuzumab-Derived scFv and Shiga-Like Toxin 2 Subunit A Against Breast Cancer: An In Silico Study |
| title_short | Design of a Humanized Immunotoxin Based on Pertuzumab-Derived scFv and Shiga-Like Toxin 2 Subunit A Against Breast Cancer: An In Silico Study |
| title_sort | design of a humanized immunotoxin based on pertuzumab derived scfv and shiga like toxin 2 subunit a against breast cancer an in silico study |
| topic | breast cancer shiga-like toxin 2 subunit a herceptin her2 bioinformatics immunotoxin |
| url | http://jmums.mazums.ac.ir/article-1-21452-en.pdf |
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