Biomimetic Nanovaccine Integrating Dendritic Cell Exosomes with Tumor Cell Membranes for Sustained Prophylaxis Against Glioblastoma

ABSTRACT Glioblastoma (GBM), one of the most aggressive and lethal brain tumors, remains incurable with a poor clinical prognosis. Cancer vaccines hold great potential for preventing malignant tumors, including GBM. However, conventional GBM vaccines face significant limitations, such as inefficient antigen delivery, safety concerns, and high production costs. Here, we have successfully developed a natural vaccine (DEX/GM) based on dendritic cell‐derived exosomes (DEX) coated with glioblastoma cell membranes (GM) that can efficiently stimulate systemic antitumor immune responses via enhancing antigen uptake by antigen‐presenting cells (APCs) and enabling sustained antigen release. The high density of tumor‐associated antigens on the cell membrane surface, combined with the intrinsic immunogenicity of DEX, promotes long‐term immune memory. Following an optimized three‐dose vaccination regimen, DEX/GM significantly induced cytokine expression and triggered the generation and activation of immune cells, including cytotoxic T cells, mature dendritic cells, and memory T cells. Importantly, this vaccination schedule demonstrated superior preventative GBM effects in mice, as all vaccinated mice survived up to 150 days even when challenged up to three times via intracranial injection of exponentially growing GL261‐luc GBM tumor cells. Therefore, our all‐natural tumor vaccine may offer a versatile strategy for the prevention of GBM, and potentially other malignant tumors, paving the way for promising future clinical applications.