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Activated T cell-derived extracellular vesicles (ATEVs) are a naturally occurring acellular immunotherapy being developed for the treatment of "immune cold" tumors, including glioblastoma, pancreatic, and breast cancers. Derived from ex vivo activated CD3+ T cells, these nanoscale vesicles carry a cargo of double-stranded genomic DNA enriched in genes related to the antigen processing and presentation (APP) pathway, along with granzyme B. ATEVs selectively accumulate in lymphoid tissues and tumors, where they are internalized by dendritic cells and tumor cells. Mechanistically, granzyme B within the ATEVs facilitates the disruption of the recipient cell's nuclear membrane, allowing for the intranuclear transfer and subsequent transcriptional expression of the EV-associated DNA. This process restores tumor immunogenicity by upregulating MHC-I/II expression and enhancing antigen presentation, thereby driving robust T cell activation and synergizing with checkpoint inhibitors like anti-PD1.
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