Engineering Dendritic Cells and Their Exosomes for Gene Therapy in Glioblastoma: Emerging Strategies and Translational Perspectives
Alper Demirezen* and Soner devrim
ABSTRACT
Glioblastoma (GBM) is the most aggressive and malignant primary cancer of the nervous system and is highly heterogeneous in terms of tumor phenotype. Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that are components of the innate immune system and coordinate the adaptive immune response; however, their function is impaired in the GBM tumor microenvironment (TME). DC-derived exosomes (DEXs) contain APCs and co-stimulatory molecules; they have emerged as cell-free immunotherapeutic vesicles offering potential advantages in terms of stability, safety, and manufacturability. Engineering strategies are being developed through ongoing research. The ability of DEXs to carry tumor antigens, siRNA, miRNA, mRNA, CRISPR/Cas components, cytokines, and targeting ligands engages immune activation through genetic transfer methods. This review article summarizes the biological rationale for DEX-based gene therapy in GBM, targeting blood-brain barrier permeability, the development of engineering strategies, preclinical findings, and GMP principles.
