Next-generation dendritic cell and exosome vaccines in NSCLC: integrating personalized medicine, nanotechnology, AI, and microfluidics for enhanced immunotherapy

Lung cancer remains the leading cause of cancer-related mortality, and non-small cell lung cancer (NSCLC) accounts for most cases. Despite advances in immune checkpoint inhibition, many patients do not respond, prompting interest in Dendritic Cell (DC) vaccines and DC-derived Exosome (DEX) platforms as personalized immunotherapeutic strategies. This narrative review examines the current clinical status of DC and DEX vaccines in NSCLC. It distinguishes therapeutic DEX products from tumor-derived extracellular vesicles, circulating diagnostic biomarkers, and exosome-mimetic nanoparticles, which differ in source, function, production, and regulation. PubMed, Google Scholar, and ClinicalTrials.gov were searched from 2000 to 2026; no formal risk-of-bias assessment or dual screening was performed, and selection bias cannot be excluded. No head-to-head clinical comparison of DCVs and DEX vaccines exists in NSCLC, and neither is supported by phase III data. We assess four enabling technologies, microfluidics, AI, nanoparticle engineering, and personalized medicine, and identify unresolved obstacles, including absent validated predictive biomarkers, lack of DEX-specific Good Manufacturing Practice (GMP) and potency standards, inter-batch variability, regulatory ambiguity, high costs, and biological heterogeneity, before proposing an explicitly hypothetical closed-loop approach. Clinical translation requires standardized methodology, validated biomarkers, GMP-compliant production, prospective trials in earlier-stage disease, and direct comparison of DCV and DEX platforms.