Journal of Vaccine Research 2024, Vol.14, No.3, 147-156 http://medscipublisher.com/index.php/jvr 149 The translated antigen is then presented on the surface of APCs via major histocompatibility complex (MHC) molecules. This presentation is crucial for the activation of T cells. CD8+ cytotoxic T cells recognize the antigen-MHC complex and are activated to kill cancer cells displaying the same antigen. Meanwhile, CD4+ helper T cells enhance the cytotoxic activity of CD8+ T cells and stimulate B cells to produce antibodies against the antigen. This coordinated immune response leads to the targeted destruction of cancer cells and the establishment of immune memory, providing long-term protection against tumor recurrence (Vishweshwaraiah and Dokholyan, 2022). 2.3 Comparison with other immunotherapies mRNA vaccines offer several advantages over other forms of cancer immunotherapy, such as DNA vaccines, peptide vaccines, and adoptive cell transfer therapies. Unlike DNA vaccines, mRNA vaccines do not integrate into the host genome, eliminating the risk of insertional mutagenesis. This safety feature, combined with the fact that mRNA vaccines are non-replicating, makes them a more attractive option for cancer therapy (Pardi et al., 2020). Compared to peptide vaccines, mRNA vaccines can encode full-length proteins, allowing for the presentation of multiple epitopes from a single antigen. This enhances the breadth of the immune response, making it more effective against heterogeneous tumor cell populations (Tan et al., 2023). Additionally, mRNA vaccines can be rapidly synthesized and scaled up, offering a significant advantage in terms of production and deployment, especially for personalized cancer treatment where the vaccine needs to be tailored to individual patients (Miao et al., 2021). Adoptive cell transfer therapies, such as CAR-T cell therapy, involve modifying a patient's T cells to express receptors specific to cancer antigens and reinfusing them into the patient. While highly effective for certain cancers, these therapies are complex and costly, and they can cause severe side effects like cytokine release syndrome. In contrast, mRNA vaccines are less complex to produce and administer, have a favorable safety profile, and can be combined with other treatments to enhance their efficacy (Duan et al., 2022). 3 Advances in mRNA Vaccine Research for Breast Cancer 3.1 Preclinical studies and milestones Preclinical studies have laid the groundwork for the development of mRNA vaccines in breast cancer treatment. Early research focused on identifying suitable tumor-associated antigens (TAAs) and optimizing mRNA vaccine formulations to enhance their stability and immunogenicity. Significant milestones include the development of nanoparticles (NPs) for delivering mRNA vaccines to dendritic cells (DCs) in lymph nodes, which demonstrated enhanced antigen-specific cytotoxic T lymphocyte responses and significant tumor inhibition in triple-negative breast cancer (TNBC) models (Liu et al., 2018). Another key achievement was the identification of immune subtypes and biomarkers for assessing mRNA vaccine suitability. Research revealed three immune subtypes among breast cancer patients, with certain subtypes showing a tumor microenvironment conducive to immunotherapy. This discovery has informed the selection of antigens and the design of personalized mRNA vaccines (Li et al., 2022). Additionally, advancements in mRNA modifications and delivery systems have addressed challenges related to mRNA instability and inefficient in vivo delivery. These innovations have significantly improved the efficacy of mRNA vaccines in preclinical models, paving the way for clinical trials (Miao et al., 2021). 3.2 Clinical trials and outcomes The translation of mRNA vaccines from bench to bedside has been marked by several important clinical trials. These trials have evaluated the safety, immunogenicity, and efficacy of mRNA vaccines in breast cancer patients. One notable trial involved an mRNA vaccine targeting the MUC1 antigen in combination with an immune checkpoint inhibitor (CTLA-4 blockade), which showed promising results in enhancing anti-tumor immune responses in TNBC patients (Liu et al., 2018). Another significant study focused on the development of personalized mRNA vaccines. Researchers used RNA sequencing to identify patient-specific neoantigens and formulated vaccines targeting these neoantigens. This
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