INTERNATIONAL CONGRESS OF
PharmacoGenetics
mRNA-Based Cancer Vaccines: A Novel Approach to Target Tumor-Specific Antigens Through Immune Activation
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Neda Zahmatkesh,1,*
1. Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
- Introduction: In recent years, mRNA vaccine technology has emerged as a transformative platform in immunotherapy, notably following its success in infectious disease prevention (e.g., COVID-19). Its high versatility, safety profile, and rapid production potential make it an attractive strategy for cancer treatment. Cancer cells often express tumor-specific antigens (TSAs) or tumor-associated antigens (TAAs) that can be targeted by the immune system if presented effectively. The objective of this review is to evaluate current advancements in mRNA vaccine development for cancer immunotherapy, focusing on strategies that enhance immune recognition of tumor-specific antigens and trigger robust antitumor immune responses.
- Methods: An extensive literature search was conducted using PubMed, Scopus, and Google Scholar databases. Keywords included "mRNA cancer vaccines," "tumor-specific antigens," "neoantigen vaccines," "immune activation," and "cancer immunotherapy". Articles published between 2019 and 2025 were prioritized. Both original studies and systematic reviews were analyzed to capture the evolving landscape of mRNA-based cancer vaccine research. A total of 47 relevant articles were selected after initial screening from an initial pool of 83 publications.
- Results: mRNA cancer vaccines work by delivering synthetic messenger RNA encoding tumor antigens into host cells, where it is translated into proteins that are subsequently presented via MHC molecules, triggering cytotoxic T lymphocyte (CTL) and helper T cell responses. Multiple studies have shown that personalized mRNA vaccines encoding neoantigens — unique antigens derived from individual tumor mutations — can elicit strong, specific immune responses. Notable examples include: Moderna’s mRNA-4157 in combination with immune checkpoint inhibitors (e.g., pembrolizumab), which demonstrated improved relapse-free survival in melanoma patients (Moderna & Merck, 2022–2023). BioNTech’s BNT122, evaluated in pancreatic and colorectal cancers, showed immune activation in early clinical trials. Advancements in lipid nanoparticle (LNP) delivery systems have improved mRNA vaccine stability and tissue targeting. Moreover, research is focusing on self-amplifying mRNA (saRNA) platforms to reduce dosing requirements while enhancing immune activation. Combination approaches — such as mRNA vaccines with PD-1/PD-L1 inhibitors — have yielded promising synergistic results in both animal models and human trials. However, challenges remain, including identifying optimal antigens, avoiding immune tolerance, and overcoming tumor-induced immunosuppression in the tumor microenvironment. Efforts are ongoing to incorporate adjuvant sequences and immune-stimulatory motifs into the mRNA construct to further boost efficacy.
- Conclusion: mRNA vaccines targeting tumor-specific antigens represent a powerful and adaptable tool in cancer immunotherapy. Their capacity for rapid design, scalability, and individualized targeting makes them ideal for personalized oncology. While clinical data is still emerging, early-phase trials show promising safety and immunogenicity profiles. As delivery technologies and neoantigen prediction algorithms advance, mRNA cancer vaccines are poised to become a cornerstone of next-generation cancer treatments, especially when combined with other immunotherapeutic strategies.
- Keywords: mRNA Cancer Vaccine, Tumor-Specific Antigen, Neoantigen, Immunotherapy
