Ex Vivo mRNA-loaded Dendritic Cell Vaccines for Cancer Immunotherapy

This scoping review examines the role of ex vivo dendritic cell (DC) mRNA vaccines in cancer immunotherapy from 2015 to 2025, with a focus on their dominance in glioblastoma trials and strategies to enhance immunogenicity and delivery. Analyzing 32 clinical trials identified through PubMed and ClinicalTrials.gov, the review highlights the vaccines’ mechanisms, safety profiles, and clinical progress, particularly in brain/central nervous system cancers (18/32 trials). Key strategies include antigen engineering with tumor-associated antigens (e.g., Wilms’ tumor 1, telomerase reverse transcriptase, and pp65) and personalized neoantigens, improved antigen processing through lysosomal-associated membrane protein sequences and PD-L1/L2 silencing, and combination therapies with immune checkpoint inhibitors, cytokines, chemotherapy, and cellular therapies (24/32 trials). Delivery optimization, including intradermal administration and preconditioning with tetanus–diphtheria toxoid or lymphodepletion, addresses migration challenges but reveals gaps in standardization. Future directions involve integrating DC vaccines with other modalities and leveraging machine learning for personalized regimens.