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  3. Vol. 16 No. 1 (2025): Continuous Volume
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Vol. 16 No. 1 (2025)

March 2025

Precision Immunotherapy for NSCLC: Multi-epitope Peptide Vaccine Targeting VEGF-A, TGF-β and MAGE-A3 Increases Antitumor Key Cytokine Balance

  • Vida Mokhtari
  • Mehrdad Hashemi
  • Sayeh Jafari Marandi
  • Ali Jebali
  • Maliheh Entezari

Archives of Advances in Biosciences, Vol. 16 No. 1 (2025), 2 March 2025 , Page 1-21
https://doi.org/10.22037/aab.v16i1.50519 Published: 2025-11-19

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Abstract

Introduction: Lung cancer remains the leading cause of cancer-related mortality worldwide, underscoring the urgent need for advancements in treatment options.  Although, current standard interventions, including surgery, radiotherapy and chemotherapy are widely employed, a significant number of patients experience relapses, highlighting the critical demand for innovative therapeutic strategies. This study was conducted to develop and evaluate a novel multi-epitope peptide vaccine designed from VEGF-A, TGF-β and MAGE-A3 markers, with the aim of enhancing therapeutic efficacy. Lung cancer remains the leading cause of cancer-related mortality worldwide, underscoring the pressing need for more effective therapeutic interventions. Although current standard treatments—including surgery, radiotherapy, and chemotherapy—are widely utilized, a substantial proportion of patients experience disease recurrence, highlighting the necessity for innovative therapeutic strategies. In this study, we developed and evaluated a novel multi-epitope peptide vaccine constructed from VEGF-A, TGF-β, and MAGE-A3 markers, with the objective of enhancing therapeutic efficacy.

Materials and Methods: Optimal epitopes from VEGF-A, TGF-β, and MAGE-A3 were systematically identified and selected, and subsequently conjugated using a KKK linker to form the final multi-epitope vaccine construct. Two groups of BALB/c mice were immunized with the peptide at concentrations of 10 mg/mL and 100 mg/mL, following an immunization protocol that included three weekly administrations. In the fourth week, spleen tissue was collected from the mice to assess the expression levels of IFN-γ, IL-4, IL-6, TNF-α, and IL-10 cytokine genes, thereby enabling a comprehensive evaluation of the immunogenic and functional efficacy of the peptide vaccine.

Results: Bioinformatics evaluations have revealed a promising multi-epitope peptide vaccine,SVRGKGKGQKRKRKKSKKKHHMVKISGGPHISYPPKKKRLESQQTNRRKKRALD.

This peptide notably enhances the expression of key cytokine genes, including TNF-α, IL-6, IFN-γ, IL-4 and IL-10 among the group that received the vaccine at a dose of 10. Even more pronounced levels of gene expression were observed at the higher dose of 100.

Conclusion: This multi-epitope peptide demonstrates considerable potential to elicit a robust immune response and effectively target cancer cells. We strongly recommend conducting further supplementary tests to evaluate its efficacy and possible side effects.

Keywords:
  • Multi epitope Peptide Vaccine
  • NSCLC
  • Cytokine genes
  • Immunotherapy
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How to Cite

Mokhtari, V., Hashemi, M., Jafari Marandi, S., Jebali, A., & Entezari, M. (2025). Precision Immunotherapy for NSCLC: Multi-epitope Peptide Vaccine Targeting VEGF-A, TGF-β and MAGE-A3 Increases Antitumor Key Cytokine Balance. Archives of Advances in Biosciences, 16(1), 1–21. https://doi.org/10.22037/aab.v16i1.50519
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