Jul 2026· Signal Transduction and Targeted Therapy· Vol 11· 1 citation· 509 references
Medicine
TL;DR
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.
Abstract
Despite advancements in therapeutic cancer vaccines, clinical translation has been hindered by limited efficacy, with Sipuleucel-T remaining the only FDA-approved therapeutic cancer vaccine to date. However, recent advances in personalized mRNA vaccines, such as Moderna’s mRNA-4157 and BioNTech’s autogene cevumeran, have demonstrated significant reductions in recurrence risk and improved survival across several cancer types, renewing optimism in the field. Personalized cancer vaccines leverage patient-specific tumor antigens to initiate potent and targeted immune responses. This review outlines various classes of personalized vaccines, including DNA-, mRNA-, peptide-, dendritic cell-, and whole-cell-based platforms, and examines the immunological challenges they face, such as tumor heterogeneity, immunosuppressive microenvironments, and inadequate immune memory. To address these limitations, both conventional and nanotechnology-enhanced delivery systems have been developed. Notably, nanovaccines constructed from lipid-polymer hybrids, biomimetic membranes, and stimulus-responsive materials enable codelivery of neoantigens and immunostimulatory agonists, promoting enhanced lymph node targeting, dendritic cell activation, and antigen cross-presentation. Furthermore, biomimetic formulations incorporating autologous tumor membranes preserve native antigenic diversity and allow dynamic adaptation to evolving tumors. When integrated with artificial intelligence for antigen selection and multiomics for patient stratification, these platforms accelerate vaccine design and improve precision. Combination regimens with immune checkpoint inhibitors or other agents further potentiate efficacy and promote durable antitumor immunity. Increasing clinical evidence, especially in melanoma and pancreatic cancer, underscores the potential of these strategies to induce long-term protection and reduce recurrence. Overall, next-generation personalized cancer vaccines are advancing the transition from reactive treatment to proactive, precision-controlled cancer immunotherapy.
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.
Dianzhe Tian, Xin-Shi Li, Zuyi Yang et al.· Frontiers in Pharmacology· 0 citations
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
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
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.
Although cancer vaccines have been proposed for decades, their clinical outcomes have remained largely unsatisfactory. Over the past decade, progress in deciphering the interaction between the immune system and cancer, along with widespread adoption of high-throughput sequencing technologies and improved MHC-peptide binding affinity prediction, have revitalized interest in cancer vaccine development. Nanomaterials benefit from the integration of tunable composition, modular architecture, and immunologically relevant dimensions, which collectively enable the rational design of immunomodulatory strategies tailored on demand, ensuring the reliable induction of antitumor immune responses. Given the spatiotemporal nature of immune responses, multifunctional nanomaterials can be further engineered to enable multivalent antigen presentation and controlled vaccine trafficking, thereby confining antitumor immune activation to desired contexts and minimizing off-target immune-related toxicities. Beyond conventional discussions of antigen delivery, this review emphasizes how rational nanomaterial design can be leveraged to regulate multiple stages of the cancer-immunity cycle, providing an updated perspective on the development of next-generation cancer vaccines. This Review will systematically summarize recent advances in nanomaterial-based cancer vaccines and discuss the key challenges and future directions in this rapidly evolving field.
Haixue Jia, Q. Fu, Dianyu Wang et al.· Biomaterials Science· 0 citations
