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Ad-TRAIL + CpG (also known as Ad5-TRAIL/CpG) is an experimental combination immunotherapy designed for the treatment of solid tumors, specifically renal cell carcinoma and prostate cancer. It consists of two primary components: a replication-deficient recombinant adenovirus (Ad5) encoding the TNF-related apoptosis-inducing ligand (TRAIL) and immunostimulatory CpG-containing oligodeoxynucleotides (CpG ODN). The therapy is administered intratumorally to leverage a dual mechanism of action. The adenoviral component induces direct apoptosis in tumor cells by expressing TRAIL, which binds to death receptors. Simultaneously, the CpG ODN component serves as a Toll-like receptor 9 (TLR9) agonist, activating local dendritic cells. These activated dendritic cells engulf the apoptotic tumor debris, migrate to lymph nodes, and cross-present tumor antigens to CD8+ T cells, thereby generating a robust, systemic antitumor immune response and long-lasting immunological memory. Research conducted at the University of Iowa has demonstrated its potential to eradicate both primary tumors and distant metastases in preclinical models.
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