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MTG201 is a novel investigational gene therapy designed for the treatment of various cancers, including malignant pleural mesothelioma and prostate cancer. It utilizes a replication-incompetent adenoviral vector (type 5) to deliver the Reduced Expression in Immortalized Cells/Dickkopf-3 (REIC/Dkk-3) tumor suppressor gene into cancer cells, where DKK3 expression is typically downregulated. The increased expression of REIC/Dkk-3 in cancer cells triggers immunogenic cell death selectively in these cells via endoplasmic reticulum stress-induced apoptosis. This process not only directly kills tumor cells but also stimulates anti-tumor immunity by activating dendritic cells and natural killer (NK) cells while suppressing regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC). As a result, MTG201 can work synergistically with immune checkpoint inhibitors such as nivolumab. The drug has been granted orphan drug designation by the US FDA for malignant mesothelioma and is under clinical investigation for other indications such as prostate cancer, with preclinical studies ongoing for liver and bladder cancers[1][4][5][6][8].
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