It is suggested that the effectiveness of mRNA cancer vaccines depends not only on selecting the right antigens but also on delivery methods that modulate the immune response and reshape the tumor microenvironment.
Abstract
Cancer remains a major global health challenge, and traditional treatments often involve significant toxicity and limited benefits for patients with advanced-stage disease. mRNA vaccines have recently emerged as a promising approach in cancer immunotherapy due to their flexibility in design, rapid production, and suitability for personalized treatment. This review summarizes the molecular basis, main classifications, and mechanisms of action of mRNA vaccines for cancer therapy and systematically discusses progress in strategies for delivering tumor-specific antigens, tumor-associated antigens, and immunomodulatory factors. Special attention is given to advances in delivery technologies, especially lipid nanoparticle (LNP) systems, and their potential applications across various cancers. We suggest that the effectiveness of mRNA cancer vaccines depends not only on selecting the right antigens but also on delivery methods that modulate the immune response and reshape the tumor microenvironment. Melanoma is a prime candidate for prioritizing the research and development of mRNA cancer vaccines, given the current clinical landscape. Furthermore, major challenges that continue to limit progress include insufficient stability, suboptimal delivery efficiency, uncontrolled immunogenicity, and the difficulty of overcoming tumor heterogeneity. This review aims to serve as a useful reference for further development and clinical translation of mRNA cancer vaccines.
Next-generation personalized cancer vaccines are advancing the transition from reactive treatment to proactive, precision-controlled cancer immunotherapy, and when integrated with artificial intelligence for antigen selection and multiomics for patient stratification, these platforms accelerate vaccine design and improve precision.
L. Ye, GuoWei Zhao, Jiaxiu Ma et al.· Signal Transduction and Targ...· 1 citation
It is proposed that the future maturation of PCVs will require a coordinated process across five interconnected dimensions: advances in neoantigen prediction technologies, rapid delivery of PCVs to patients, an increase in anticancer efficacy through combination therapy strategies, establishment of cost-effective manufacturing processes, and regulatory innovation.
Seongje Cho, Jisun Lee, Young-Min Lee et al.· Experimental and Molecular M...· 0 citations
mRNA has emerged as a transformative platform in vaccine oncology, offering rapid design, non-acquired security and powerful activation of adaptive immune. Despite encouraging preclinical and clinical results, challenges such as efficient distribution, tumor immune evasion, and patient-specific antigen selection limits their widespread clinical translations. We systematically reviewed preclinical studies and clinical trials examining mRNA vaccines in various cancer, including glioblastoma, melanoma, lungs, breasts, digestive systems, ovarian, prostate, kidney and hematological malignancies. Comparative analysis were carried out between mRNA, DNA and peptide vaccine platforms. Additionally, we critically examined the tumor resistance mechanism and proposed the next generation strategies, including the nanometer-based delivery system, self-ampliming mRNA (saRNA), and bioinformatics-operated antigen discovery, which are using single-cell sequencing. Clinical trials continuously display the safety and immunity of mRNA vaccines, with a strong induction of CD8+ T cell reactions and cancer types. However, efficacy outcomes remain variable, with strongest responses in high-mutation-burden tumors such as melanoma and NSCLC, and limited benefit in low-mutation-burden tumors such as prostate and ovarian cancers. Our ideological structure introduces the integration of mRNA vaccines with car-T cells and monoclonal antibodies to remove tumor immune resistance. In addition, we present an accurate algorithm, taking advantage of scRNA-seq for patient-specific neostagen selection, and highlight the benefits of saRNA in increasing antigen expression with low dosage requirements. mRNA vaccine represents a rapidly growing frontier in cancer immunotherapy, yet their success will depend on addressing biological and translation obstacles. This review synthesizes not only current clinical evidence, but also provides innovative conceptual models and future instructions that may redefine the design of the next generation cancer vaccines. By bridging advances in nanotechnology, computational biology and adaptive clinical trial designs, the task offers a roadmap to achieve sustainable, individual and widely accessible cancer immunotherapy.
Head and neck cancer (HNC) remains a significant global health burden, with high morbidity and mortality despite advances in conventional therapies. The immunosuppressive tumor microenvironment (TME) and tumor heterogeneity have limited the efficacy of current treatments, driving the exploration of novel immunotherapeutic strategies. Immune checkpoint inhibitors (ICIs) have established a role in recurrent/metastatic HNC, yet response rates remain modest and resistance is common. In this context, mRNA vaccines have emerged as a transformative approach due to their flexibility, rapid development, and ability to induce potent, antigen-specific immune responses. This review provides a comprehensive analysis of the application of mRNA vaccines in HNC immunotherapy, focusing on three major antigen sources: tumor-associated antigens (TAAs), tumor-specific neoantigens (TSAs), and virus-associated antigens such as HPV E6/E7. We examine the advantages and limitations of different delivery platforms-including lipid nanoparticles (LNPs), self-amplifying RNA (saRNA), and ex vivo dendritic cell (DC)-mRNA vaccines-and discuss their integration with other modalities such as ICIs, chemotherapy, and radiation therapy. Preclinical and clinical data demonstrate that personalized neoantigen vaccines can elicit robust T-cell responses and improve survival outcomes, particularly in HPV-positive HNSCC. However, challenges such as tumor heterogeneity, inefficient delivery, immunosuppressive TME, manufacturing complexity, and lack of predictive biomarkers hinder widespread translation. Future directions include the development of "off-the-shelf" shared-antigen vaccines, next-generation delivery systems with enhanced targeting, combination regimens, and biomarker-guided patient selection. With continued innovation in mRNA technology and translational research, mRNA vaccines hold immense potential to redefine the treatment paradigm for HNC, offering durable immune protection and improved clinical outcomes.
Linrong Wu, Hongshuai Liu, Zhikai Wang et al.· Critical reviews in oncology...· 0 citations
Traditional treatments for lung cancer include surgery, radiotherapy, chemotherapy, and targeted therapies (such as Erlotinib, Gefitinib, and Crizotinib), as well as immunotherapy (such as Nivolumab and Pembrolizumab). However, these approaches face challenges such as drug resistance, limited efficacy, and significant side effects, making it difficult to improve long-term prognosis. Therefore, tumor vaccines, as a novel immunotherapy strategy, have become a focus of research, aiming to precisely activate anti-tumor immune responses and address the shortcomings of existing treatments. In recent years, mRNA vaccine technology has developed rapidly, especially following the successful application of COVID-19 vaccines, demonstrating its immense potential for rapid development and large-scale production. mRNA cancer vaccines induce durable anti-tumor immune responses and reshape the tumor microenvironment by delivering mRNA encoding tumor-specific antigens, enabling targeted therapy. Through the dual synergistic pathways of direct local modulation by the vector/encoded factors and secondary effects mediated by antigen-specific T-cell activation, the tumor microenvironment is reshaped, thereby inducing durable antitumor immune responses. Against this background, this review systematically evaluates the current status and prospects of mRNA vaccines in lung cancer treatment, with a focus on their progress in precisely modulating the tumor microenvironment, identifying novel tumor antigens, discovering immune biomarkers, and related clinical studies. Additionally, the review discusses the process optimization of lipid nanoparticle (LNP) delivery systems, aiming to provide theoretical support and practical guidance for the development of safe and effective therapeutic vaccine platforms for lung cancer.
Hao Wu, Ruiqi Weng, Siyi Gu et al.· Frontiers in Immunology· 0 citations
Overall, cancer vaccines are unlikely to become universal stand-alone treatments for advanced solid tumors, and their most credible role may emerge in molecularly selected patients, adjuvant therapy, minimal residual disease, virus-associated malignancies, and rational combinations with checkpoint inhibitors or tumor microenvironment-modulating agents.
Dario Rusciano· Frontiers in Cell and Develo...· 0 citations
