Nanovaccines for lung cancer: Platforms, mechanistic insights, and translational challenges

Lung cancer remains a global health challenge, with high mortality rates and frequent resistance to conventional therapies. In recent years, nanovaccines-based immunotherapy has emerged as a promising frontier, harnessing advances in nanotechnology to enable precise delivery of tumor-associated antigens, potentiate immune activation, and overcome barriers imposed by the tumor microenvironment. This review synthesizes current knowledge and recent progress in the field, highlighting several nanovaccine platforms from mRNA and protein constructs to biomimetic designs, which have demonstrated preclinical efficacy against both primary and metastatic lung cancer. We illustrate how innovations can elicit robust polyclonal T cell responses and remodel the immune landscape within tumors, including co-delivery of antigens and adjuvants, use of patient-derived materials, and integration of multi-omics. Furthermore, the combination of nanovaccines with current therapies, including immune checkpoint inhibitors, cell-based therapies, and gene-modulating strategies, offers new avenues for enhancing therapeutic outcomes. Despite these advances, several challenges remain, including barriers of large-scale manufacturing, safety assessment, regulatory approval, and the need for personalized optimization. Ongoing research and clinical studies will be essential to translate these experimental successes into personalized treatments for patients with lung cancer. Nanovaccine immunotherapy stands poised to become a transformative component in the evolving landscape of lung cancer management.