Nanovaccines in Cancer Immunotherapy: Lymph Node-Targeted Strategies and Mechanistic Insights

BACKGROUND: Cancer immunotherapy has been a rapidly growing therapeutic approach, with nanovaccines offering new opportunities to improve antigen delivery and activate immune responses. Nevertheless, traditional cancer vaccines are generally under-immunogenic and ineffective in lymphoid targeting. This article reviews progress in nanotechnology-based vaccine platforms, with a special emphasis on lymph node-targeting nanovaccines for cancer management and therapy. METHODS: We systematically reviewed the recent literature on nanovaccine delivery systems, including liposomes, polymeric nanoparticles, and mRNA-based formulations. The emphasis was on immunological mechanisms, antigen presentation pathways, and lymphatic targeting strategies. RESULTS: Nanovaccines can deliver tumor antigens and adjuvants together to lymphoid tissues, enhancing antigen uptake, dendritic cell activation, and T-cell priming. Systems, such as lipid nanoparticles, artificial dendritic networks, and CpG- or STING-charged nanocarriers, have been shown to exhibit enhanced therapeutic performance in both preclinical and early clinical trials. mRNA-4157 and BNT111 are clinical candidates showing encouraging results in melanoma and other cancer trials. CONCLUSION: Nanovaccine platforms can potentially overcome some constraints of conventional vaccines by enhancing lymph node targeting, antigen stability, and immunogenicity. Further research in this field could further advance targeted cancer immunotherapy.