Tehran University of Medical Sciences

Science Communicator Platform

Share By
Enhancing Antitumor Efficacy of Muc1 Mrna Nano-Vaccine by Ctla-4 Sirna-Mediated Immune Checkpoint Modulation in Triple Negative Breast Cancer Mice Model Publisher Pubmed



Monfaredan A ; Sen S ; Fathi NK ; Tastekin D ; Hosseininasab A ; Bozbey HU ; Oncul O
Authors

Source: International Journal of Molecular Sciences Published:2025


Abstract

Immunotherapy, particularly approaches that combine tumor-specific vaccines with immune checkpoint modulation, represents a promising strategy for overcoming tumor immune evasion. While most mRNA-based cancer vaccines focus solely on antigen delivery, there is a need for platforms that simultaneously enhance antigen presentation and modulate the tumor microenvironment to increase therapeutic efficacy. This study presents a novel dual-nanolipid exosome (NLE) platform that simultaneously delivers MUC1 mRNA and CTLA-4-targeted siRNA in a single system. These endogenous lipid-based nanoparticles are structurally designed to mimic exosomes and are modified with mannose to enable selective targeting to dendritic cells (DCs) via mannose receptors. The platform was evaluated both in vitro and in vivo in terms of mRNA encapsulation efficiency, nanoparticle stability, and uptake by DCs. The co-delivery platform significantly enhanced antitumor immune responses compared to monotherapies. Flow cytometry revealed a notable increase in tumor-infiltrating CD8+ T cells (p < 0.01), and ELISPOT assays showed elevated IFN-γ production upon MUC1-specific stimulation. In vivo CTL assays demonstrated enhanced MUC1-specific cytotoxicity. Combined therapy resulted in immune response enhancement compared to vaccine or CTLA-4 siRNA alone. The NLE platform exhibited favorable biodistribution and low systemic toxicity. By combining targeted delivery of dendritic cells, immune checkpoint gene silencing, and efficient antigen expression in a biomimetic nanoparticle system, this study represents a significant advance over current immunotherapy strategies. The NLE platform shows strong potential as a modular and safe approach for RNA-based cancer immunotherapy. © 2025 Elsevier B.V., All rights reserved.
Related Docs
View other Related Docs
1. Blockade of Ctla-4 Increases Anti-Tumor Response Inducing Potential of Dendritic Cell Vaccine, Journal of Controlled Release (2020)
2. Nanomedicine for Improvement of Dendritic Cell-Based Cancer Immunotherapy, International Immunopharmacology (2020)
3. Boosting Breast Cancer Immunotherapy Through Targeted Sirna Delivery and Sequential Chemotherapy, Journal of Drug Targeting (2025)
Experts (# of related papers)
View all Related Experts
Fatemeh Atyabi (6)
Farid Dorkoosh (2)
Other Related Docs
4. Anti-Ctla-4 Nanobody As a Promising Approach in Cancer Immunotherapy, Cell death & disease (2024)
5. Silencing Adenosine A2a Receptor Enhances Dendritic Cell-Based Cancer Immunotherapy, Nanomedicine: Nanotechnology# Biology# and Medicine (2020)
6. Cd73 Specific Sirna Loaded Chitosan Lactate Nanoparticles Potentiate the Antitumor Effect of a Dendritic Cell Vaccine in 4T1 Breast Cancer Bearing Mice, Journal of Controlled Release (2017)
7. Lung Cancer Vaccine Strategies: Exploring the Spectrum From Traditional to Rna-Based Platforms, Frontiers in Bioengineering and Biotechnology (2025)
8. Mrna Cancer Vaccines From Bench to Bedside: A New Era in Cancer Immunotherapy, Biomarker Research (2024)
9. Tumor-Associated Macrophages, Nanomedicine and Imaging: The Axis of Success in the Future of Cancer Immunotherapy, Immunotherapy (2017)
10. New Approaches in Cancer Immunotherapy: Review Article, Tehran University Medical Journal (2018)
11. Nanotechnology-Based Pd-L1 Sirna Codelivery Systems for Improving Cancer Immunotherapy, Journal of Drug Targeting (2026)
12. In Silico Analysis of Vegfr2 and C-Met in Consideration With Immunologic Facts: Implications for Mrna Vaccine Design Against Breast Cancer, International Immunopharmacology (2025)
13. Hybridization of Polysaccharide/Lipid Composite-Based Nanovesicles for Precise Delivery of Drug/Gene/Protein in Immunotherapy: A Promising Paradigm for Precision Cancer Therapy, Carbohydrate Polymers (2026)
14. Smart Bio-Encapsulation for Immunotherapy, Smart Nanomaterials for Bioencapsulation (2022)
15. Nanoparticles in Cancer Immunotherapies: An Innovative Strategy, Biotechnology Progress (2021)
16. Chitosan-Based Materials and Strategies in Immunotherapy and Synergistic Immunochemotherapy: A Focus on Gene-Based Immunoregulation and Car-T and Adoptive Cell Transfer, Carbohydrate Polymer Technologies and Applications (2025)
17. Polymeric Nanoparticles for Dna Vaccine-Based Cancer Immunotherapy: A Review, Biotechnology Letters (2023)
18. Genetically Modified Immune Cells Targeting Tumor Antigens, Pharmacology and Therapeutics (2020)
19. Antibody Targeted Delivery of Lipid Nanoparticles for Rna Therapeutics to Immune Cells, International Journal of Biological Macromolecules (2025)
20. Development of a T Cell-Targeted Sirna Delivery System Against Hiv-1 Using Modified Superparamagnetic Iron Oxide Nanoparticles: An in Vitro Study, Journal of Pharmaceutical Sciences (2022)