Volume 35, Issue 245 (5-2025)
J Mazandaran Univ Med Sci 2025, 35(245): 15-29 |
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Ghesmati Z, Ahmadi K, Nezafat N, Vahedi F, Taheri-Anganeh M, Khatami S H, et al . Design of a Humanized Immunotoxin Based on Pertuzumab-Derived scFv and Shiga-Like Toxin 2 Subunit A Against Breast Cancer: An In Silico Study. J Mazandaran Univ Med Sci 2025; 35 (245) :15-29
URL: http://jmums.mazums.ac.ir/article-1-21452-en.html
URL: http://jmums.mazums.ac.ir/article-1-21452-en.html
Zeinab Ghesmati 
, Khadijeh Ahmadi , Navid Nezafat , Farzaneh Vahedi , Mortaza Taheri-Anganeh , Seyyed Hossein Khatami , Hasan Ghasemi , Rahmatollah Soltani , Vahid Zarezade , Ahmad Movahedpour , Ahmad Movahedpour
, Khadijeh Ahmadi , Navid Nezafat , Farzaneh Vahedi , Mortaza Taheri-Anganeh , Seyyed Hossein Khatami , Hasan Ghasemi , Rahmatollah Soltani , Vahid Zarezade , Ahmad Movahedpour , Ahmad Movahedpour
Abstract: (101 Views)
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.
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.
Type of Study: Research(Original) |
Subject:
Biotechnology
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