Engineering Dendritic Cell-Derived Extracellular Vesicles for Gene Delivery in Glioblastoma: Emerging Strategies and Translational Perspectives
Alper DEMİREZEN *
Kocaeli University, Kocaeli, Türkiye.
Soner DEVRİM
Kocaeli University, Kocaeli, Türkiye.
*Author to whom correspondence should be addressed.
Abstract
Glioblastoma (GBM) is the most aggressive adult-type diffuse glioma and remains difficult to treat because of extensive infiltration, molecular and cellular heterogeneity, therapeutic resistance, and an immunosuppressive tumour microenvironment. Dendritic cells (DCs) coordinate antigen presentation and T-cell priming, but their abundance and function are limited in GBM. Dendritic cell-derived extracellular vesicles (DC-EVs), including preparations commonly described as dendritic cell-derived exosomes, retain selected antigen-presenting and immunoregulatory molecules and can be engineered to carry nucleic acids, proteins, antigens, and targeting ligands. This narrative review evaluates the biological rationale, engineering approaches, delivery barriers, preclinical evidence, clinical precedents, and manufacturing requirements relevant to DC-EV-mediated gene delivery in GBM. Particular attention is given to blood-brain and blood-tumour barrier heterogeneity, endosomal escape, cargo quantification, biodistribution, potency, and safety. Current evidence supports the feasibility of DC vaccination in GBM and the clinical manufacture of DC-EVs in other cancers, but no engineered DC-EV gene-delivery product has established clinical efficacy in human GBM. Translation therefore requires reproducible product definition, mechanism-linked potency assays, relevant orthotopic and immunocompetent models, quantitative biodistribution, and controlled clinical evaluation.
Keywords: Glioblastoma, dendritic cells, extracellular vesicles, exosomes, gene delivery, cancer immunotherapy, blood-brain barrier, RNA therapeutics