Genprex Reports New Pre-Clinical Data Showing Strong Anti-Tumor Effect Of TUSC2 In Combination With PD-1 Checkpoint Blockade In Lung Cancer
- Category: DNA RNA and Cells
- Published on Monday, 03 April 2017 10:10
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AUSTIN, TX, USA I April 2, 2017 I Genprex, Inc. announced new pre-clinical data which reveal that TUSC2 (formerly known as FUS1, the active anti-cancer agent in OncoprexTM) in combination with PD-1 checkpoint inhibition has a significantly greater anti-tumor effect in lung cancer than either agent alone. The research also shows that TUSC2 in combination with PD-1 blockade has synergistic activity in upregulating natural killer (NK) cells, correlated with prolonged survival in mice. The research was presented at the 2017 Annual Meeting of the American Association of Cancer Research in Washington, D.C.
TUSC2 is a tumor suppressor gene that is lacking in cancer cells of many different cancer types, including non-small cell lung cancer (NSCLC). It is a pan-kinase inhibitor that has been shown in-vivo to affect cell proliferation and programmed cell death. PD-1 is a protein found on certain types of T cells, which are part of the immune system. Because PD-1 prevents T cells from attacking other cells, including in some cases cancer cells, inhibiting PD-1 can facilitate the immune response to cancer.
The study, conducted by Jack A. Roth, M.D., F.A.C.S., and his team at The University of Texas MD Anderson Cancer Center in Houston, evaluated the immune response of TUSC2 alone and in combination with anti-PD-1 agents across five independent experiments in two syngeneic mouse models, including a model of lung metastasis. There was a statistically significant reduction in the rate of tumor growth when treated with TUSC2 alone compared with a no treatment control or anti-PD-1 alone, and an even more significant reduction when treated with TUSC2+anti-PD-1 compared with control or anti-PD-1 monotherapy. The greatest reduction in tumor volume occurred when mice were treated with TUSC2+anti-PD-1 compared with TUSC2 or anti-PD-1 alone.
TUSC2 alone or in combination with checkpoint blockade (anti-PD-1 and/or anti-CTLA4) significantly prolonged mouse survival in the NSCLC metastasis model compared to checkpoint blockade alone. The greatest increase in survival was seen with TUSC2 combined with checkpoint blockade. The treatment response was associated with high infiltration of NK cells and CD8 T cells, and low infiltration of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment.
"These data suggest that TUSC2 could become a promising new treatment approach to lung cancer, particularly in combination with approved PD-1 checkpoint inhibitors, such as nivolumab," said Julien Pham, M.D., MPH, COO of Genprex. "The data further support a direct effect of TUSC2 on various immune cells which induces a synergistic antitumor immune response. We will continue to evaluate this relationship and its effects on cancer."
"Lung cancer is the leading cause of cancer deaths in the U.S. and there remains a high unmet need for many patients who are unresponsive to currently available treatment options, especially among those with late-stage non-small cell lung cancer," according to Rodney Varner, CEO of Genprex. "These data complement results from ongoing clinical trials that show the reinforcing effect of TUCS2 therapy when used in combination with other targeted treatments."
Genprex is utilizing its proprietary gene therapy platform to develop Oncoprex as a targeted treatment option suitable for a majority of non-small cell lung cancer (NSCLC) patients. Research has shown that over 80% of cancer cells of many types of cancer, including NSCLC, lack a tumor suppressor gene called TUSC2 (formerly known as FUS1), a pan-kinase inhibitor which has been shown in-vivo to affect cell proliferation and programmed cell death. Oncoprex is an optimized TUSC2 gene encapsulated in a fatty, positively charged nanovesicle (a nanoscale hollow sphere) injected intravenously, which can specifically target cancer cells and insert wild-type TUSC2 into cellular DNA, effectively increasing expression of the TUSC2 protein and promoting tumor cell death.
Oncoprex immunogene therapy is designed to 1) target and kill cancer cells, 2) block mechanisms that create drug resistance, and 3) stimulate natural immune responses against cancer. Oncoprex combines features of gene therapy and immunotherapy in that it up-regulates the tumor suppressor gene TUSC2, increases the anti-tumor immune cell population, and down-regulates PD-L1 receptors thereby boosting the immune response to cancer.
Oncoprex has shown synergistic anti-cancer activity when combined with EGFR inhibitors in pre-clinical and clinical studies. Pre-clinical data also indicate that Oncoprex can be combined with several other approved cancer therapies, including targeted and immunotherapies, to improve efficacy with minimal side effects and become a complementary therapy for other cancer treatments.
Genprex is a privately held, clinical-stage biopharmaceutical company developing novel gene therapies to improve outcomes of and expand access to promising targeted and immunotherapies for cancer. The company is also working with world-class institutions and collaborators to in-license and develop additional drug candidates. Genprex controls a portfolio of issued and pending patents covering tumor suppressor genes, nanovesicle delivery systems, and manufacturing processes. The company was founded in 2009 and is headquartered in Austin, Texas. For more information, please visit www.genprex.com or www.facebook.com/genprexinc.