Biomimetic and personalized nanovaccines in cancer immunotherapy: Design innovations, translational challenges, and future directions
Suling Xu, Haitao Yang, Boris Minev, Wenxue Ma
Abstract
• Biomimetic nanovaccines enhance tumor-specific antigen delivery and adaptive immune priming. • RBC, exosome and immune cell membrane coatings improve circulation longevity and targeting. • Personalized mRNA and peptide nanovaccines demonstrate synergy with immune checkpoint blockade. • GMP manufacturing, regulatory complexity, and safety profiling remain key translational barriers. • AI-guided neoantigen design and modular and microfluidics support scalable personalized vaccine production. Personalized nanovaccines represent advancing frontier in cancer immunotherapy by integrating patient-specific tumor antigens with biomimetic delivery systems to enhance immune activation, targeting precision and clinical efficacy. Biomimetic platforms including exosome-, red blood cell (RBC)-, and immune cell membrane-coated nanoparticles, as well as artificial antigen-presenting cell (aAPC) systems, recreate native biological interfaces to improve antigen presentation, macrophage polarization, and adaptive immune priming. Despite significant progress, major translational challenges remain, including incomplete mechanistic understanding, regulatory complexity, and manufacturing scalability. This review synthesizes recent advances in biomimetic and personalized nanovaccine design, highlighting clinical progress in lipid nanoparticle (LNP)-based vaccines such as BNT111 and mRNA-4157, emerging innate immune adjuvants including Toll-like receptor (TLR) and stimulator of interferon genes (STING) agonists, and rational combination strategies with immune checkpoint blockade. Key safety and quality consideration including immunotoxicity, off-target immune activation, and batch heterogeneity are critically evaluated alongside emerging engineering solutions. Finally, future directions integrating AI-guided neoantigen prediction, modular microfluidic manufacturing, and multi-omic biomarker frameworks are discussed to accelerate next generation cancer nanovaccine translation.