REIC Technology

MTG Biotherapeutics, located in San Diego, is a clinical-stage biotechnology company dedicated to the development of a novel immuno-oncology therapy based on REIC expression technology to treat unmet needs. MTG’s REIC expression technology combines the concepts of gene therapy, oncolytic viral vectors and immuno-oncology treatment for an effective method to selectively kill cancer cells without significant side effects. This approach selectively destroy the cancer, and debulk tumors safety, while activating the immune system to specifically target that cancer type to attack residual disease. Founded as a spin out in 2014 from our Japanese parent company, Momotaro-Gene, MTG has moved the program quickly into a Phase 2 clinical stage with ongoing US based trials in prostate cancer. MTG-201 directly induces selective apoptosis in localized prostate cancer cells and stimulates the immune system to produce cancer specific activated cytotoxic T-lymphocytes (CTL) and natural killer (NK) cells. MTG-202 combines the technology of MTG-201 with an conditionally replicate competent viral vector to target other more aggressive cancers, such as Mesothelioma, HCC and invasive Bladder cancers. MTG has also received Orphan Drug Designation in 2015 for the treatment of Malignant Mesothelioma from the US FDA

Reduced Expression Immortal Cells (REIC) Protein

Reduced expression immortal cells (REIC) is a protein, produced by the REIC or Dickkopf-3 gene, that is deficient in many types of cancer cells. Expression of REIC can induce cell death through apoptosis in cancerous cells, but REIC does not initiate apoptosis. Rather, REIC is an integral part of the apoptosis mechanism that, when absent, prevents the cell from completing the apoptotic mechanism. REIC is present in all normal human cells, and thus over expression in normal cells does not induce cell death. Forced expression of REIC is lethal to certain cancer cells that are immortalized due to hypermethylation of the Dickkopf-3 gene resulting in REIC protein deficiency, including those associated with Prostate Cancer, Malignant Mesothelioma, Hepatocellular Carcinoma (HCC), Invasive Bladder Cancer, RCC, NSCLC, SCLC and other cancer types.

Mechanism of Action

MTG is developing an immune oncology platform of products that is based on replacement of REIC protein in cancer cells that are immortalized due to hypermethylation of the Dickkopf-3 gene. Cancer cells that are immortalized through genetic damage to the Dickkopf-3 gene cannot complete the apoptosis cycle due to a deficiency in REIC protein. Forced expression of REIC induces apoptosis in cancer cell lines lacking endogenous REIC expression through a mechanism that involves c-Jun-NH2-kinase activation, mitochondrial translocation of Bax, and reduction of Bcl-2. REIC may also interfere with Wnt/β-catenin signaling via Wnt receptors. MTG technology temporarily replaces the REIC protein within these cancers using a viral vector technology that is harmless to normal cells.

By selectively inducing apoptosis in cancer, REIC vector technology helps release cancer antigens that are taken up by dendritic cells. Through this process it has been demonstrated that REIC induces upregulation of the immune system against the cancer. The resulting cancer specific Cytotoxic T-cell Lymphocytes (CTLs) and Natural Killer T-cells (NKTs) have been demonstrated in both nonclinical and clinical studies. This immune stimulatory affect has been observed in both preclinical and clinical studies conducted to date. Synergistic effects with anti-PD1 antibody has also been demonstrated in nonclinical models.